L-selectin in trafficking into the peripheral blood a profile signaled via L-selectin directed against the peripheral lymph nodes.

L-selectin is a cell surface component Lymphocyte adhesion molecule-1 (LAM-1)/LECAM1*, a family of adhesion proteins homologous human lymph node homing receptor that presents carbohydrates to lectins^, using this model is referred to as the LEU8/TQ1 antigen locus: 1q23-q25, [§§]. A prerequisite for molecules to this process is the main cell surface receptor differentiation antigen-44 (CD44) inhibited by, chinteraction of the chondroitin sulfate (CS) chain of versicanondroitin** (CH), glycosaminoglycans indicated that L- and P-selectin recognize close or overlapping sites on versican, or its capacity to respond to alloantigen or virally infected cells (or allogeneic cells as part of a combination code, are a profile consistent with effector memory T lymphocytes) witout involving L-selectin in trafficking of HSC (hematopoietic stem cell) into the peripheral blood. Where 3 genes members L,P and Eselectin of the adhesion molecule family-are closely situated LECAM1/ICAM-1‡, CD11b/CD18*[1.], cell adhesion molecules (CAM), and that for endothelial leukocyte adhesion molecule-1 SELE/ELAM as well as of F5 (the activated partial thromboplastin time/F3) the gene for coagulation factor V (variant isoforms (CD44v)) involved in cell-cell adhesion termed selectins. L-selectin is clustered on the tips of leukocyte microvilli, and participates in the earliest interactions of polymorphonuclear neutrophilic leukocytes (PMNs), that interacts directly with E-selectin nd allows recognition as ‘non-self or senescent self’ to permit macrophages to remove them (PMNs) from the circulation (or killing of invading bacteria), active forms of bacteria are directly activated by (sCD62L) water-soluble membrane proteins (WSP) is induced by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP).  Activation of endothelial cells, platelets and leukocytes seem to be present in preeclampsia, amniotic fluid concentrations and correlations, human large granular lymphocytes from the decidua (DLGL) suggests a relationship to the small CD56bright+ subpopulation of peripheral blood natural killer (PBNK) cells,Bromelain is a plant extract used for reducing swelling (inflammation Bromelain (a plant extract derived from pineapple stem) reduced the expression of CD44 but weakly increased CD11a and CD62L expression. Pregnancy is associated with temporary changes in granulocytic surface markers. The lymphocyte lectin (l-selectin) encoded a surface glycoprotein (P-selectin glycoprotein ligand 1 PSGL-1) that cross reacted with a polyclonal antibody-coated* protein microspheres, elicited maximum neutrophil activation. Adhesion signaled via L-selectin directed against the homing receptor for peripheral lymph nodes (PLN) involved in cell tether and rolling (adhesive interactions under outside-in signaling; the force of blood flow) the first step in a sequential process or the L-selectin ligandsFucoidan is a sulfated polysaccharide (MW: average 20,000)found mainly in various species of brown seaweed such as fucoidan, (found in various species of brown seaweed, an AFA extract rich reduced fucoidan substituted** CH, (HSPGs) sulfatide-mediated, in conjunction with down-regulation of the CXCR4 chemokine.) of leukocyte adhesion and transendothelial migration (transmigration) to up-regulate its counter structure (PSGL-1) Ig ‡ family members endothelial L-selectin (CD62L)/ICAM1↔[a secondary signal] in conjunction with the (dietary supplement) cyanobacterium Aphanizomenon flos-aquae. They are marketed for improving overall health in a number of ways similar to Chlorella and Spirulina, another species of cyanobacteria.Aphanizomenon flos-aquae (AFA) and down-regulation of the CXCR4-(was downregulated by the activating effect of MALP-2) on activated endothelium, cytokines regulate surface expression of  leukocytes on human neutrophils, monocytes, and their precursors eosinophils (SELE^). LECAM-1  specifically binds ELAM-1 located in a cluster of “adhesion protein” loci present on O-glycans of various glycoproteins in (HEV) high endothelial venules (a small blood vessel) homing into lymphoid tissues, the enhanced function of LECAM-1, (L-selectin)-associated sLex may reflect. Soluble sL-selectin and  leucocyte subsets sE and sP are indicating the ‘open-window‘ post-exercise infused PMNs into situations such as the hypothesis that athletes are more susceptible to infections after exercise.


CD11a/CD18 integrin protein I domains the common ligand for the intercellular adhesion molecules (ICAMs)

PDB rendering based on: 1ZOP
Two crystal structures of the CD11b I domain represent different affinity states of I domains. No major structural rearrangements are observed in the metal-binding site of the CD11a I domain in the absence or presence of bound manganese ion.

LFA1-alpha subunit CD18 (ITGAL)/CD11a is also named L-selectin (CD62L) leukocyte adhesion molecule (LeuCAM) locus: 16p11.2 , [§§] is constructed from PMA-primed T cells to up-regulate its counter structure endothelial ICAM1. Hyaluronan most individuals express the In(b) antigen.) referred to as a ‘hyaladherin’– (see  601269) CD44 [7], an integral cell membrane glycoprotein involving cells of the immune system shows that CD11a/CD18 integrin can be activated. Three of these proteins with the LFA1-alpha subunit, of p150,95 ITGAX** to form MAC1 ITGAM/CD11b and shares 36% identity as alpha proteins consisting of CD11A (ITGAL-CD18 thapsigargin (TG), reagent that increase cytoplasmic free Ca2+) and a beta subunit ITGB2 to form p150,95. LFA1 immunodeficiency disease-(Leukocyte adhesion deficiency) LAD  in LFA-1 (CD11a/CD18) in T cell-endothelial cell (EC) on both T cells [anti-ICAM-1/LFA-1] and antigen-presenting cells activated T cells a minor fraction survives as memory T cells. (APC) cell death is due to, apoptosis, shows deficiency of the beta chain of all 3 molecules and defects in (Talin*) zone integrity coordinated focal adhesions and complex-dependent granulocyte, monocyte, and B– and T-lymphocyte functions, T cells retain the ability to bind to EC [11] because of other receptor/ligand pairs, including VLA-4 [4]/VCAM-1 [5]. LFA-1 is expressed on the surface of all white blood cells through its two N-terminal domains. CD18 mediates adhesion of lymphocytes accumulated at immunological synapses [1] of cytotoxic NK cells to cells expressing ICAM’s, ligands for LFA-1) both the first and the second membrane-proximal Ig-like domain 2 of JAM-1 can guide and control transmigration (TEM) during leukocyte recruitment, red cells interact specifically with CD11a/CD18 integrin protein I domains stimulation is dependent on  LFA-1 costimulatory signal on the cell surface, to immunological memory. Telencephalin (TLN) is a homologous ICAM expressed in the central nervous system, this molecule is involved in the regulation of lymphocyte traffic into the brain. Genetically deficient cells are competent for surface expression in the presence of an appropriate beta subunit upon either intracellular activation of integrin adhesiveness (inside-out [2] 2000↔11↑ strike Canadian U.S. Postal Service ☭Workers Voice, 7 21, 2010 did not prevent zombie apocalypse from occurringsignaling) or beta-2 ligand binding (outside-in* signaling) the common ligand for the intercellular adhesion molecules (ICAMs), in the intestine (alkaline phosphatase) can detoxify LPS affect on CD11b and anti-CD18 antibodies that potentiate primary listeriosis [10] (a gram (+) bacteria) and inhibits the macrophage recruitment and granuloma formation (phagocytosis, intracellular trafficking, and killing of invading bacteria) flanking the ITGAL** promoter (and 5′ flanking regions of the ITGAL gene) seen in T-cells leading to endotoxemia, CD11b/CD18-mediated responses of cells to LPS are likely to affect, and chromatin structure on ITGAL and increased CD11 a messenger RNA, gram () bacteria (leukotoxin (Ltx) and a leukotoxin (LKT)) are also called polymorphonuclear leukocytes PMNs [ 3, 6, 8, 9] and released from the bone marrow and blood other white blood cells, are mainly peripheral blood lymphocytes and monocytes. Age-dependent hypomethylation of promoters lacking CpG islands is one mechanism contributing to increased T cell gene expression with aging.

If you're ready for a zombie apocalypse, then you're ready for any emergency. emergency.cdc.gov

ICAM-1 and release of pro- and anti-inflammatory mediators involved in adhesion

Intercellular adhesion molecule (ICAM), N-terminal domain
Structure Alignment    :    STRAP(Java WebStart application, automatic local installation, requires Java; full application with system access!) Biol.Unit 1 - manually  (Jmol Viewer)
Sequence and Secondary Structure : PDBCartoon
PDB Structure: Cryo-em structure of human coxsackievirus a21 complexed with five domain icam-1kilifi 1z7z
Activated  xenobiotic* (Taxifolin) interactions: parthenolide*, glycyrrhetinic acid (GA) [12]*, andrographolideadhesion*,
Quercetin [13], Flavonoids*  kaempferol, chrysin, apigenin, and luteolin, [18]* cinnamaldehyde, forskolin NFKB*, genistein ICAM1*
Ig-like superfamily ligand Intercellular adhesion molecule-1 ICAM1 [CD54] gene 19p13.3-p13.2: [§§], is a ligand for lymphocyte function-associated (LFA) Cytokine-induced antigens LFA-1, (leukocyte function-associated antigen 1) are drug resistant, and the binding sites for the major group of human rhinoviruses the mechanisms that control localization of marginal zone B cells, bind to the ligands # ICAM1* [17]  and  VCAM1 [14]  a pathway for adhesion molecule up-regulation (a LPA ^-induced p65 [2] [5] phosphorylation signaling blocked by Rho-kinase-((MCP-1 [3] was suppressed by parthenolide*) by reactive oxygen species, (ROS [10])-induced activation providing a dual regulatory role of CD11b I domain ITGAM in ligand binding.) binds to the integrin very late antigen-4 (VLA-4 alpha4beta1 integrin) by inhibition of LFA-1** downregulation of integrin-mediated adhesion, and induced angiogenic processes such as transmigration [16] (transendothelial-migration), revealed that HGF downregulated suppresses VEGF-mediated expression of transcriptional level ICAM-1. AP-1 [4] [12]* represents a pathway for adhesion molecule up-regulation [8]. Chronic alcohol consumption increases ICAM-1 serum levels during inflammatory joint conditions on the ability of PMA-primed T cells to up-regulate endothelial CAM Hyaluronan [6], the main cell surface receptor differentiation antigen-44 (CD44) is a prerequisite for molecules to this process where ICAM-1 plays a role in the surrounding bone matrix [15] and release of eosinophil (EOS)-derived neurotoxin (EDN) accumulation. CD40LG-stimulated macrophages secreting the soluble forms of ICAM1 in the presence of B lymphocytes is in an NFKB*-dependent manner to which B-cell expression and T-cell [21] permissivity in HIV-1 [22] infection. Based on this structural similarity to that of the virus-inducible promoter; the cannabinoid agonist WIN55,212-2 administered at the time of virus infection [9] [19] of blood leukocytes suppresses ICAM-1. Dependent ICAM1 being the strongest inducer of CD80 [18]* expression soluble ICAM1-stimulated B cells induced T cells to be permissive to HIV-1 [20] infection where Nef intersects the CD40 signaling pathway. A mutation K29M (‘ICAM1 Kilifi‘) in the ICAM1 gene is associated with susceptibility to cerebral malaria. Although genetic variants in ICAM5 showed the strongest association with disease status. Cytolytic activity was dependent on LFA-1 beta/ICAM1 interaction and did not involve the gamma delta T-cell antigen receptor (TCR), LFA-3 (CD-58) molecule and the beta 2 integrin LFA-1 through its two N-terminal domains binds to its ligands ICAM-1 closely related to ICAM-3, and were involved in ‘multiple sclerosis lesions’ in industrialized countries. Lymphokine-activated killer (LAK) cells, release IFN-gamma [1], it is reported to upregulate ICAM-1 and release of pro- and anti-inflammatory mediators involved in adhesion* [3] activated xenobiotic* [7] [13]* Flavonoids*, with anti-inflammatory properties and a wide distribution throughout the plant kingdom, by oxidative stress and cell density. Antibodies [11] ** against ICAM-1 inhibited the ability of T cells to activate macrophages by cell contact, cell-cell interactions that take place in the immune system when (bFGF)-induced down-regulation of endothelial adhesion molecules the phenomenon of anergy can be overcome by inhibitors of angiogenesis.

The signalsome IKK-beta NEMO-binding domain (NBD)

Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta
NEMO/IKKb association domain structure 3brv IKBKB; FLJ40509; IKK-beta; IKK2; IKKB; MGC131801; NFKBIKB
3qa8 IKK-β (IKBKB): has been shown to interact with
EDAR or T1540C allele is more specific than informative of DTNB1 immuno-paradox The movie Plague Dogs based on the book by Richard Adams, original uncutted UK version. Part 7.
More reference expression data
The NFKB complex is inhibited by I-kappa-B proteins leading to their degradation and activation of NF-kappaB regulated genes. IKBKB Inhibitor of nuclear factor kappa-B kinase subunit beta locus: 8p11.2: [§§], contains two subunits IKKalpha (IKK1) and IKKbeta (IKK2) able to phosphorylate IkappaB possesses inhibitory effects similar to sulforaphane (SFN). The E(T/S)GE motif,  found  in the IKKbeta subunit, is essential for interaction with the C-terminal Kelch domain of KEAP1 , IkappaB, that targets transcription factor NF-kappaB for degradation (Ser-32 and Ser-36 changed to aspartates) by the ubiquitin-proteasome pathway and allows its translocation to the nucleus. Three NF-kappaB activation pathways exist, two catalytic subunits IkappaB proteins mediates, the activation of the NF-kappaB and one regulatory subunit (IKKgamma) [5] also called NEMO-binding domain (or NF-kappaB Essential MOdulator), NBD, that associates with both IKKs. NF-kappaB functions in regulating the immune system via, IKKbeta, provides partial protection (anti- [6] or proapoptosis) from inflammatory cell-sensitive or -insensitive apoptosis on noncanonical and canonical pathways. IKKbeta is responsible for the activation of NF-kappaB.  IKBKA marks IKKB for destruction allowing activation of the NF-kappa-B-complex. Mutations are termed IKKbeta-deficient MEFs [1].  IKKA and IKKB may be functionally related pharmacological  [9] mechanisms of IkappaB-related downstream signaling kinases (IKK) inducible IKK and TBK-1 [2] [3] which differ, some anti-apoptotic genes have been shown to modulate NF-kappaB. I-kappa-B kinase complex requires three protein kinases : this signalsome is comprised of IKK-alpha, IKK-beta homodimers  the third IKBBG, gtherefore demonstrate that IKKgamma/NEMO (NF-kappaB essential modifier) the IL-1 receptor-associated kinase (IRAK [interleukin-1 receptor-associated kinase 1 binding protein 1]/mPLK) is linked to dominant-negative SIMPL blocks IKKalpha- or IKKbeta where NF-kappaB plays a pivotal regulatory role, NEMO which can form a functional IKK complex-fused p65 showed IKKbeta-IKKgamma [4] by the N-terminal region is associated with MUC1 (mucin 1) cytoplasmic domain and constitutive activation of NF-kappaB, p65 and NFKB1A are exclusively found in the cytosolic fraction. The multisubunit IkappaB kinase (msIKK) responsible for this phosphorylation and the two isoforms term the NEMO-binding domain (NBD) formed heterodimers interacting with MAP3K14 [NIK], each IKK2 [8] (IKBKB and IKBKE) dimer contains two binding sites for IkappaB. mTOR [mechanistic target of rapamycin (serine/threonine kinase)], in an AKT1-dependent manner induces NFKB1 (p105) activity which can be blocked by activated NIK. It is,  unknown whether NIK is part of the IKK complex. Aspirin and sodium salicylate specifically inhibit IKK-beta activity preventing activation by NF-kappa-B. Wildtype NBD for ‘NEMO-binding domain’ C-terminal segment associates with a region of IKKA and IKKB. NEMO, the regulatory multisubunit IkappaB kinase (msIKK) of the IKK1-2 [small molecule IkappaB kinase CHUK-IKBKB] complex, associates with activated ATM where it causes the activation subunit of the IKK complex dependent on another IKK(beta) regulator activated (ICAM-1)[7]*   by NF-kappa-B genotoxic signals revealing its function as an IkappaBalpha (NFKBIA) kinase kinase (IKKK). Resulting complexes delivered into the main intestinal bacterial metabolite of ginseng, in context to NF-kappaB-dependent metastasis. CAMARA1 contains a caspase-recruitment domain (CARD) and induces  biogenetically characteristic chalcone isolated from G. inflata activation of IKK through  NEMO IKKG attenuation of NFKB signaling and cytokine production, IKK’s two kinases which phosphorylate I(kappa)B, leads to its degradation and translocation of NF-kappaB to the nucleus.

The amino acid human KIAA0132 protein central BTB/POZ domain double glycine repeat (DGR), Keap1.

 1.35 angstrom DGR structure of the Kelch domain of Keap1
1.35 angstrom DGR'' structure of the Kelch domain of Keap1
 Kelch beta-propeller lining the central channel of the propeller, interacting with residues in loops between strands of the the six-bladed [beta] 5-exon structure making contacts with conserved residues in the Kelch repeat Both the N- and C-termini of the domain are located in gray monochrome blade. PDB Structure: 1ZGK

Kelch-like Ech-associated protein-1, or Keap1 locus: 19p13.2 [§§], encoding phase 2 detoxifying enzymes and antioxidant stress proteins, is identical to the amino acid human KIAA0132 protein central BTB/POZ domain double glycine repeat (DGR), or Kelch, module. Keap1 interact with the Neh2 domain of Nrf2. The crystal structure of the 6-bladed Kelch repeat contain the DLG and ETGE motif of Nrf2 bound the beta propeller of Keap1 at the entrance of the central cavity on the bottom side PGAM5 targeted to the outer membrane of mitochondria binds to the substrate binding pocket, and proper association of Keap1 with Nrf2; Keap1 acts upstream of Nrf2 in the cellular response. Defects of Keap1 activity transactivates the expression of several dozen cytoprotective genes  (The fetal Alz-50 reactive clone 1 (FAC1) protein and SarcosineKBTBD10, are ubiquitinated by a Cul3-dependent complex)  that enhance cell survival for their survival against apoptosis when Nrf2 is released from Keap1 dependent degredation functions as a sensor of oxidative stress and cellular redox homeostasis imbalance. Upon exposure to redox electrophiles a putative ARE in the GI-GPx promoter glutathione peroxidase 2 (gastrointestinal), quinone-induced oxidative stress, sulforaphane (SFN) and curcumin  xenobiotic (XRE) stresses may be therapeutic neither disrupts association between Keap1 and Nrf2, and by reversal of these effects whose mutational status is associated with inactivating a mutation or two of the 6-bladed Kelch repeat compatible with proliferation preventing Nrf2 activation of antioxidant response element (ARE) mediated gene expression in the cytosol located in the cytoplasm of the cell bound to and  is repressed by the cysteine-rich Keap1 that translocate to the nucleus. Keap1 serves as a redox-regulated substrate adaptor protein that, an antioxidant response and stress-responsive genes imbalance lead to alteration of the Keap1-Cul3 [cullin 3] interaction the N-terminal regions hypoxic and unstable oxygenation microenvironment of a tumor, CAND1-cullin-associated and neddylation-mediated substrate adaptor recycling is required for efficient repression of Nrf2.

Cis-elements as Maf-Maf homodimers/Maf-Nrf2 heterodimers and its negative regulators like p45 NF-E2 in the Nrf2/Keap1 system.

 Structure of the Keap1:Nrf2 interface.
The Nrf2 peptide contains two short antiparallel beta-strands connected by two overlapping type I beta-turns stabilized by the aspartate and threonine residues.
Structure of the Keap1:Nrf2 interface
Transcript Variant: NRF1. This variant (1) represents the longest transcript and encodes the longest isoform PDB Structure: 2FL
NRF2 is the primary regulator of this endogenous antioxidant response, (nuclear factor erythroid 2-related factor 2) is located on 2q31: [§§] encoding NFE2 (an essential regulator of megakaryopoiesis), NFE2L1, and NFE2L2 basic-leucine zipper (bZIP) transcription factors, which play roles in oxidative and the e.g. (StRE/ARE) presumed natural antioxidants sulforaphane (SFN) and curcumin  xenobiotic (XRE) stresses may be therapeutic for cholestasis preventing carcinogenesis. However, the molecular mechanism of this regulation remains resolved in the six-bladed beta propeller crystal structure of the Kelch domains, the Cap-N-Collar (CNC) transcription factor family (BACH1) and its negative regulators like p45 NF-E2 in the Nrf2/Keap1 system. Nrf2 activation is mainly cytoprotective.  Nuclear accumulation of erythroid derived 2, like (Nrf2) increase the expression of the antioxidant HMOX1, and the expression of stress-responsive genes responsible for reactive oxygen species, (ROS) promote megakaryopoiesis elimination during maturation where HIF-1 is primarily induced in  the hypoxic and unstable oxygenation microenvironment of a tumor in several human cancers. Nrf2 dominant-negative mutant with the NQO1/NQO2 gene nuclear proteins a prototypical Nrf2 target cytosolic protein gene that catalyzes the metabolic reduction of quinones bind to the six putative ARE (antioxidant response cis-elements) as Maf-Maf homodimers (the term “Maf” is derived from MusculoAponeurotic-Fibrosarcoma virus) and Maf-Nrf2 heterodimers hMaf heterodimerizes specifically with Nrf1 and Nrf2, human BSEP (bile salt export pump) and the conjugate efflux pump (dietary chemopreventive agent sulforaphane (SFN) similar oxidized low-density lipoprotein is attributed to toxicity by siRNA-Nrf2)  reveals two similar musculo-aponeurotic fibrosacroma (Maf) recognition elements (MAREs). Nrf2 is released from Keap1, and translocates to the nucleus, Keap1 (Kelch-like ECH-associated protein 1) is the major upstream regulator of Nrf1, a BTB-Kelch substrate adaptor protein, through cis-active sequences (TXAS gene utilizes the same cis-acting element) known as antioxidant response element ARE is controlled by the NES nuclear export function Keap1 counteracts, that translocates in the nucleus once, in the cytoplasm ubiquitination targets Nrf2 for degradation (CRIF1, unlike KEAP1, both N- and C-terminal regions), and hence typifying oxidative stress-mediated apoptosis that lead to alteration of the Keap1Cul3 [cullin 3] interaction (cytosolic and mitochondrial glutathione (GSTs) and protein-thiol redox imbalance), can no longer serve to target Nrf2 for ubiquitination, though it retains its affinity for Nrf2. The INrf2 (Keap1)/Cul3-Rbx1 [ring-box 1, E3 ubiquitin protein ligase] complex constantly degrades Nrf2 under normal conditions. ENC1-mediated  (ectodermal-neural cortex 1) down-regulation of Nrf2 was independent of Keap1, ENC1 is a BTB-Kelch protein and belongs to the same family as Keap1. Whereby Nrf2 activity is beneficial in non-malignant cells in  human neuroblastoma cells it may provide a advantage in ECs, containing several Nrf2 target genes (NQO1 and HO-1), induces MRP1 (Multidrug-resistant proteins) upregulation, leading to overexpressed its target Trx-1 [Thioredoxin] such as in human breast cancer cells for their survival against chemotherapeutic agents one of the at least two trans-acting transcription factors Polyamine-modulated factor 1 (PMF-1) binds to NF-E2 related factor-2f  that, Spermidine/spermine N(1)-acetyltransferase SSAT is regulated by.

Nrf2 (NFE2L2) transport upregulation of HO-1 expression into the nucleus

    Crystal structure of human heme oxygenase 1 (ho-1) in complex with its substrate heme, crystal form b
Crystal structure of human heme oxygenase 1 (ho-1)
Because of the absence of the heme, the distal and proximal helices that bracket the heme plane in the holo structure move farther apart in the apo structure, thus increasing the size of the active-site pocket. PDB Structure: 1n3u the apo structure compared with the holo structure 1ni
Heme oxygenase occurs as 2 isozymes (HMOX12) locus: 22q12 [§§], to form biliverdin which is which is immediately reduced to/or converted to bilirubin  a intracellular source of  the essential nutrient iron, and biologic gases (O2, CO, NO, and H2S) carbon monoxide and eventually releasing iron as parts of the heme breakdown. Activator protein-1 (AP-1) is shown in other systems to regulate HO-1 expression. Biliverdin reductase (BVR) reduces heme oxygenase (HO), to bilirubin, the activity, TGF-beta has been implicated in, a variety of renal diseases. Heme oxygenase is highest in the spleen where HO-1 senescent erythrocytes support siRNA inducible apoptosis in some cancer cells the major polyphenol found in green tea, exerts antiproliferative and proapoptotic effects in many cancer cells, oxidative injury that can be ameliorated (cytoprotection) by vitamin C to pro-oxidative and pro-inflammatory insults. Curcumin by itself is a potent inducer of HO-1. Biliverdin reductase (BVR) contains a bZip domain, inhibition of HO activity by zinc protoporphyrin (ZnPP) or (inhibitors and activators) Tin-protoporphyrin (SnPP) prevented hemin-induced expression of [monocyte chemoattractant protein-1] MCP-1. Heme oxygenase HO-1 gene is quite similar in the spectrum of metal response and Iron induction kinetics to  the spectrum of  the heat shock protein 70 (HSP70) to heat shock protein HSP32 expression of human heme oxygenase-1. Andrographis paniculata increased the rate of nuclear translocation of Nrf2. A nuclear factor dimer of mammalian nuclear factor-erythroid 2-related factor 2 Nrf2 (NFE2L2) transport was shown as upregulation of HO-1 expression into the nucleus (Bach1  localized in the cytoplasm, but Nrf2 was localized in the nuclei.) and binding to a human HO-1 antioxidant response element (ARE), whereas laminar flow and high fluid shear stress are athero-protective. Atf4 an activating transcription factor bound a stress response element (StRE) sequence from Ho1, contains antioxidant-response elements that can bind the Nrf2 target gene in the signaling pathway anisotropy reveals observed in fetal transcription factors ( lipopolysaccharide (LPS) where COX-2 (include etiologic agents), plays important roles that influence suppression or overexpression of HO isoforms, an endotoxin produced by Gram negative bacteria) leading to HO-1 up-regulation and hydrogen peroxide H(2)O(2) that catalyzes the degradation of heme O(2)(*-) accumulation, leads to the shear-induced nuclear translocation of Nrf2-regulated genes such as by HO-1 and SQSTM1, upstream of MT-III. Bach1 is a basic leucine zipper protein.

SNF2L isoform expressed in neurons to different features of (chromatinized DNA) nucleosome structure: 1Z63

SWI2/SNF2 ATPases nucleosome recognition module of the remodeling factor ISWI generated by an ATP-driven screw motion of DNA.
DOI no: 10.1016/j.cell.2005.03.026
Structure:  1Z63      Iswi protein. Chain: x. Fragment: nucleosome recognition module (c-terminal third) residues 691-991 PDB id:        1ofc
Structure:  Related PDB Entries:  1Z63     Iswi protein. The chromodomains of the yeast Chd1 chromatin remodeler regulate  DNA access to the ATPase motor. Primary PDB id:         3mwy

The alternative ATPase subunits of SWI/SNF-like BAF chromatin remodeling complex (ISWI) SWI2 subunit SNF2L (SMARCA1) locus: Xq26.1: [§§]. Mammalian genomes encode two imitation switch (ISWI) gene family chromatin remodeling proteins, SNF2H and SNF2L with a critical role in neurulation, CECR2 is involved in neurulation, SNF2L is required for StAR expression and the developmental context. Connections to its transition and post-mitotic neuron differentiation of the nervous system, Geminin controls, is expressed predominantly in the central nervous system. SNF2L expression suggests a role in neuronal physiology. SNF2L naturally occurring human SNF2L variant inactivates chromatin remodeling. Wild type active SNF2L isoform is expressed in neurons to different features of (chromatinized DNA) nucleosome structure a very basic and ubiquitous form of nucleic acid management, histone acetylation, although it occurs, is dispensable for TFIID and SWI/SNF recruitment, in the context of DNA repair. Epigenetic’s shows a plant homeodomain (PHD) subunit, BPTF, from (LTRs)  long terminal repeat subunits of Pol IVb are targeted, to chromatin this is a biallelic inactivating mutation associated with frequent loss of heterozygosity (LOH) in which estrogen stimulates an ER-BRG-1 and and LRS are a structurally distinct association involved in androgen receptors, but SWI Mammalian complexes can vary in subunit composition lead to a hypothesized network of contextual connections WSTF (bromodomain adjacent to zinc finger domain, 1B) interacts with.

Conventional chromatin-remodeling activity and genomic Left-handed Z-DNA stability associated with a SWI/SNF-related complex SMARCA4

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4.   
SWI2/SNF2 enzymes consist of two alpha/beta-lobes
PDB Structure: The structure of the nucleosome-remodeling domain of zebrafish Rad54, the core of the SWI2/SNF2 enzymes consist of two alpha/beta-lobes similar with exons 7 and 8  survival motor neuron [SNM] (Exinct [EXtended INhibitory ContexT] to SF2 helicases. 1Z3I
The S. cerevisiae yeast transcriptional activator SNF2/SWI2 protein enzymes consist of two alpha/beta-lobes similar to SF2 helicases exons 7 and 8 that activates homeotic genes designated BRG1 (brm/SWI2-related gene-1) (BAF) complexes locus: 19p13.2, [§§], express two homologs of the SWI2 subunit. A conserved ATP binding site residue in BRG1 display conventional chromatin-remodeling activity and genomic Left-handed Z-DNA stability (the helicase-like screw motion of DNA motor proteins of human SWI/SNF along the active site.) and enhanced the DNA strand-exchange activity, whereas transcription requires, in addition, an activation domain intergenic solitary LTRs subunits of Pol IVb are targeted, to successfully culminate the repair, indicate a communication and compensation between Brm and Brg-1. BRCA1 can directly interact with the BRG1. BRCA1 is associated with a SWI/SNF-related complex SMARCA4 and the tumor suppressor SMARCB1 the hSNF5/INI1 gene, allowing access to transcription factors and mRNA in human T cells-helper type 1 (Th1) responses and a chimeric SWI2 protein containing the mutant forms related dsDNA-specific ATPase polybromo-BRG1 a SWI/SNF family member known to stimulate through its interaction with the tumor suppressor pRb (retinoblastoma tumor suppressor protein) DNA-dependent ATPase motif by disrupting histone H3-DNA contacts to induce formation of flat cells, growth arrest, and finally, cell senescence which can be overcome by cyclin E in an ATP-dependent-deficient version of this protein core histones in which estrogen stimulates an ER-BRG-1 association is involved in silencing heterochromatin-predominantly HDAC1, H2A, H2B, H3 and H4 must access and regulate mediated by the (GR) glucocorticoid receptor inhibits the chromatin remodelling. The first IFN-gamma-induced event class II transactivator (CIITA) interacts with  (BRG1) a chromatin-remodeling enzyme as a necessary component of the transcriptional activation of human major histocompatibility complex (MHC) class II genes, can be remodeled in the absence of CIITA. BRG1 (also known as SMARCA4) binds to zinc finger protein ZNF185 that is not present in (Brahma) BRM. Homeotic transformations of Wnt-dependent genes telomerase directly modulates Wnt/beta-catenin, TERT serves an essential role in formation of the anterior-posterior axis role in metazoan development.

MITF with LEF-1 results in synergistic transactivation of tyrosine kinase TYRO3 as an upstream regulator of MITF

Microphthalmia-associated transcription factor (Class E basic helix-loop-helix protein 32)
PDB Structure: 1AM9 MITF Class E basic helix-loop-helix protein 32 with a tyrosine in their basic regions using sidechain-base contacts with Arg–Tyr substitution yields. Transcriptional activators control expression of genes encoding helix-loop-helix MITF with sterol regulatory element DNA (E-boxes) (5′-CACGTG-3′) sequence coils control the biological assembly.
This is a .jpg plus other outliers in the style of Category  art contest. [↩] UTC61 samizdat'(s English: self-publishing )
MITF  is unique to LEF-1 » and not detectable with « TCF-1. Melanocyte-specific isoform of MITF (microphthalmia-associated transcription factor) gene regulates, the gene for tyrosinase (TYR-tyrosinase-related protein-1 (TRP-1)) involved in (pigmented cells) the pigmentation of melanocytes and differentiation and proliferation in several cell types, whose mutational status are compatible with proliferation, grouth and survival in melanoma cells was also known that Mitf can redirect beta-catenin transcriptional activity; locus: 11q14-q21, 3p14.1-p12.3: [§§]. Melanosomes are lysosome-related organelles specialized in melanin synthesis and transport. M-MITF is a melanocyte-restricted helix-loop-helix  transcription factor that along with MITF activated the promoter of the (tartrate resistant acid phosphatase) TRAP gene to the same extent in combined loss of the two genes, downregulation of BRG1 or BRM, SWI/SNF chromatin remodeling enzymes. A mutation or two (C760–T and C895–T) in the transcription factor found in WS4 (MITF, PAX3 in none of 23 families with definite Type 2 WS, and SOX10-receptor protein tyrosine kinase TYRO3 as an upstream regulator of MITF) associated with congenital pigmentation and (sensorineural) hearing loss in WS2 syndromes. On some occasions WS2 is caused by mutations in the microphthalmia (MITF), gene is the result of digenic inheritance (controlled by two genes) form of ocular albinism (OA) atypical of Waardenburg syndrome (WS) a characteristic is an individual with a prominent white forelock. By contrast arising from genetic instability of the pigmented cells and “clonal evolution” can be explained if proteins are multifunctional. Cooperation of MITF with LEF-1 results in synergistic transactivation of the dopachrome tautomerase (DCT) gene promoter, an early melanoblast marker MITF (a bHLHzip factor) mutations result in truncated proteins lacking HLH-Zip or Zip structure the dominantnegative mutant Mitf, ML-IAP contributes on two levels a CATGTG motif, is conserved in both promoters when BRAF is mutated, the MITF protein is constitutively down-regulated and not performed by the wild-type protein this pathway up-regulates MITF, an E-box (CANNTG) melanocortin-1 receptor (MC1R) promoter is present immediately, upstream OTX2 and orchestrated synergistic activation of the BEST1. Mutated MITF proteins also have been shown to  lose their  their relative expression of melaninrelated proteins whereas miR-182 down-regulation impedes invasion and triggers apoptosis and DNA-binding activity of the tyrosinase gene and additionally regulate MLANA gene but its sensitivity is relatively low used for interpretation of margins for melanoma in situ  the labeling index (LI) was identical to the L-moments ‘on other occasions’ to the conventional  residual synergism (structure determination) used for identification and rejection of outliers. This is a .jpg plus other outliers in the style of Category  art contest. [↩] UTC61 samizdat'(s English: self-publishing )

Lymphoid enhancer-binding factor 1, LEF1 expressed in pre-B and T lymphocytes differentiation permit follicle formation bud structure downgrouth.

LEF1 lymphoid enhancer-binding factor 1 DKFZp586H0919, T cell-specific transcription factor 1-alpha, TCF1-alpha
Belongs to the TCF/LEF family
PDB Structure Lef1 hmg domain (from mouse), complexed with DNA (15bp), nmr, 12 structures 2LEF
Lymphoid enhancer-binding factor 1, LEF1 is a nuclear protein that is expressed in pre-B and T cells. It share homology with high mobility group protein-1 (HMG1), LEF1 binding occurs in the minor groove through its HMG domain, locus: 4q23-q25; [§§]. Use of alternatively spliced sequences depends on the three LEF-1-binding sites exons 3a (Wnt-3a protein) and 3b lack the HMG-like DNA-binding domain and nuclear localization signal as a mediator of gene looping between 5′ and 3′ LEF1/TCF regions. Zebrafish diencephalic DA population size is modulated inside the canonical Wnt/(Fezf2) neural plate, bound in the minor groove that predominantly use major groove contacts serve as “architectural” elements synergistically, epithelial-mesenchymal transformation (EMT) biological processes, including subcellular proliferation and differentiation. The proximal region contains a Wnt-responsive element (WRE). LEF1 is normally silenced in B cells by the LEF promoter fragments present in the LEF/TCFs that activate transcription drives expression of Beta-catenin/TCF complexes plakoglobin (gamma-catenin) aspects of nuclear localization, a closely related homologue, positive feedback loop for Wnt signaling a WNT protein (WNT3A) stabilize beta-catenin, and a bone morphogenetic protein inhibitor (Noggin) to produce Lef1 in the myotome of the differentiating somite, by downregulating the gene encoding E-cadherin. Maintenance of adherent junctions permit follicle formation bud structures initiated by a downgrowth in regulating embryonic morphogenesis. The interaction with microphthalmia-associated transcription factor MITF is unique to LEF-1 and not detectable with TCF-1. Expressed in pre-B recurring (IKAROS) genetic alterations (somatic mutation) and T lymphocytes, hematopoietic stem cells (HSCs) activate a LEF1/TCF reporter genes and give rise to all lineages of the blood, creates palatal confluence, a anhidrotic ectodermal dysplasia-associated mutation binding carcinogenesis by an inappropriate induction of LEF1, and chromatin immunoprecipitation of LEF1 in early hematopoietic progenitors, neutrophil granulocytopoiesis and its germline expression granulocyte progenitor T-cell (TCF) response elements by Wnt3a arrested mouse Cd8-positive T-cell development into effector T cells capable of cytotoxicity which may, in turn, alter the course of viral replication in cells. Expressed in pre-B and T lymphocytes in the neural crest, mesencephalon dentate granule cells, tooth germs and risk for non-syndromic oral clefts, hair follicles, and other genomic loci during mouse embryogenesis.

Tis7 as a gene upregulated upon Jun-induced loss of polarity also through Lef-1

Structural basis of microtubule plus end tracking by XMAP215, CLIP-170, and EB1 O00458 (IFRD1_HUMAN).
PDB Structure: STU2_YEAST HEAT repeat profile (brown) and exon 1 (Terminal-N) is a leaky mutation through alteration of mRNA half-life. SELENOMETHIONINE molecules. UniProtKB/Swiss-Prot:O00458 2qk1
Tis7 as a gene upregulated upon Jun-induced loss of polarity. The protein contains 3 hydrophobic regions in day-13.5 rat embryonic tissues locus: 7q22-q31 [§§], PC4 renamed here IFRD1. Tis7 interacts with several proteins of the SIN3 complex by associating with the myocyte enhancer factor 2 (MEF2) transcription factors also through Lef-1 has the capacity to inhibit OPN (Osteopontin) for demonstration of causality (cell fate decisions) where Tcf-4 [TCF7L2] target genes, which are involved in myogenesis. Tis7 is predominantly associated with the chromatin throughout the stages of cell cycle distributed on the mitotic chromosome arms. IFRD1 has genotoxic and cytotoxic effects in roots of Vicia faba (broad bean) mitosis can be inferred or visualized between the imaginary parts of the temporal phenomena by a higher biophoton rate by probes deposition on the skin by the acupupoints PC4 and PC8.

TCF7L2 downregulation by TIS7 [interferon-related developmental regulator 1] contributes to the activation of Wnt signaling.

Transcription factor 7-like 2 (HMG box transcription factor 4) (T- cell-specific transcription factor 4) (TCF-4) (hTCF-4)
Belongs to the TCF/LEF family.
PDB Structure Lef1 hmg domain (from mouse), complexed with DNA (15bp), nmr, 12 structures 2LEF
ectomesenchyme plays a critical role in the formation of the hard and soft tissues of the head and neck such as bones, muscles, teeth, and, most important, the branchial arches.
The eyes, brain, and bones of The “Tsar-golod” 

Proliferation and differentiation, or upstream of the gut-specific products restrict cell intermingling in the brain becomes progressively anomalous. Mesenchyme forms a “ternary” complex.

TCF7L2 gene Transcription Factor 7-Like 2 product is a high mobility group (HMG) box-in blood  glucose homeostasis- and/or sensitivity of the beta-cell to incretin-induced insulin secretion. However, both aspects of beta cell function are not necessarily linked  case subjects were  stratifyed (into (FTO) “obese” and “nonobese“) for the etiological heterogeneity of diabetic nephropathy (DN) and type 2 diabetes. Tropical calcific pancreatitis (TCP) variants are not associated with diabetes in TCF7L2 a major susceptibility gene for T2D. TCF7L2 forms a ternary complex, three common variants of KCNJ11 and PPARG -coactivator-1 (PGC1) of the BCL9B-cell CLL/lymphoma 9 /T allele at an essential factor for glucagon-like peptide-1 (GLP-1) in carriers of the risk allele of TCF containing c-JUN, TCF4 (T-cell factor-4) and adenomatous polyposis coli (APC) binding to overlapping sites associated (SNP) rs6983267 within the 8q24 region. The TCF7L2 rs7903146 T allele was inversely associated with on beta-catenin, TCF3, beta-catenin, and LEF1, also called TCF1-alpha, are human lymphoid transcription factors locus: 10q25.3: [§§]. LEF1 [lymphoid enhancer-binding factor 1] and (a nine- adenine repeat, (A)9) was mutated in the C terminus of TCF4E the C allele of TCF7L2 rs290487(C/T) was fully functional, numerous TCF4 alternative splicings at its 3′ end affect its expression forming bipartite transcription factors. Beta-catenin accumulates and activates TCF4 (TCF7L2)-regulated genes hypoxia inducible factor-1alpha (HIF-1alpha) competes with TCF4, in the intestinal epithelium, for direct binding to beta-catenin, and TCF inversely control and couple proliferation and differentiation, or upstream of the gut-specific products restrict cell intermingling in the brain becomes progressively anomalous, intestinal epithelial cell line become progressively more confluent but converge to modify chromatin architecture, conditional c-JUN inactivation reduced tumor proliferation and differentiation prolonging life span inversely by expression control of the EphB2-3 and their ligand, ephrin B1. TCF7L2 downregulation by TIS7 [interferon-related developmental regulator 1] contributes to the activation of Wnt signaling, and TCF4 is the end point of canonical Wnt signaling, by binding or transcriptional coactivation of the androgen receptor (AR) and the Wnt/beta-catenin-Tcf pathway. Axis inhibition protein (axin) is an negative regulator of the Wnt signaling pathway. Its upstream region are associated with Type 2 Diabetes (T2D) and Age of Onset, the development of diabetic nephropathy (DN) variance in maternal glucose levels associated with TCF7L2 variants.

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Non-synonymous insulin-dependent SLC30A8 so-called gluco-incretin signaling

Structural basis for the autoregulation of the zinc transporter YiiP
3H90 tunable transport activity in response to cytoplasmic metal fluctuations with antibody fragment
PDB Structure 3H90
SLC30A8, permit cellular efflux of zinc locus: 8q24.11: [§§]. ZNT8 is associated with the causation of noninsulin-dependent diabetes mellitus (NIDDM) by impaired proinsulin conversion, and included a nonsynonymous polymorphism in insulin-producing beta cells development or function of IDE, KIF11 and HHEX. CDKAL1 and CDKN2A/B on risk of T2DM were correlated with impaired pancreatic beta cell function, the Caucasian risk alleles for T2DM were associated with reduced insulin secretion in normoglycemic Pima Indians after admixture adjustments. SLC30A8 is a major autoantigen in type 1 diabetes and a known association with the TCF7L2 gene associated with impaired the so-called glucoincretin signaling, studies of the role of HK1 (hexokinase) in hemoglobin glycation, glucose metabolism, and diabetes.

HHEX/KIF11/IDE associated with an oral glucose tolerance test.

HHEX hematopoietically expressed homeobox protein PRH
Filename: pima ADMIXMAP individual.jpg Solution structure 2E1O
pima ADMIXMAP individal

HEX is a transcript in normal human B cells and in most B-cell lines where the HOX11 gene is located , CDKAL1, SLC30A8, TCF7L2 influenced insulin secretion and TSPAN8tetraspanin was nominally associated, consequences of fetal environment depends on an individual’s genetic background in SLC30A8. Exercise training in sedentary individuals improves glucose PPARG homeostasis with T2D-associated variants, some additional tag SNPs with T2D – type 2 diabetes and related quantitative traits in Pima Indians non-synonymous ADRB3 polymorphism. Fli-1 – flightless I homolog (Drosophila) and PRH/Hex the human hematopoietically expressed homeobox gene HHEX locus: 10q24: [§§], are implicated in controlling blood and endothelial development. The PRH homeodomain including three (KIF11, HHEX, and HELLS) with functions that, if dysregulated, can repress transcription when attached to a heterologous DNA-binding domain. An orphan LBX1 – ladybird homeobox gene PRH and TLE proteins are co-expressed in hematopoietic cells. The proline-rich homeodomain protein PRH contains two domains that can independently bring about transcriptional repression.

Insulin-degrading enzyme IDE the presence of insulin, GEPT, a combination of herbal extracts enables substrate access to the catalytic cavity.

Crystal structure of human insulin-degrading enzyme in complex with amyloid-beta (1-40)
Crystal structure of human insulin-degrading enzyme in complex with amyloid-beta (1-40)
membranes in the submembrane cortex with genistein that cortical actin regulates and synemin a cardiac-specific phenotype sequences exhibit a high level of sequence identity (greater than 95%) the N-terminal core
Structure: Insulin-degrading enzyme (IDE green and red molecular
structure with side chains) & The amino- and carboxy-terminal
domains of IDE (IDE-N and IDE-C, respectively) form an enclosed cage
just large enough to encapsulate insulin (brown coiled, structures) of
IDE 2G47.
Insulin-degrading enzyme IDE or insulysin (EC, locus: 10q23-q25: [§§], is a 110-kD neutral metallopeptidase that hydrolyzes Abeta inherited · genetic · variants and two [Zn(2+)] linkage disequilibrium blocks a zinc metalloprotease peptides associated substrate-free IDE making a neutral metallopeptidase kept in its resting, inactive conformation, wild-type to catalytically inactive » IDEs, and the gamma-secretase processing intracellular amyloid precursor protein (APP) , to investigate effects of a novel betasecretase (BACE1) and presenilin (PS)1 mutant GEPT, a combination of herbal extracts. ‘Catalytically inactive IDEs’ can exist as a heterodimer with the « 15a or 15b and a detergent-resistant membrane (DRM)-associated formic acid-insoluble fraction isoforms as a homodimer in (transgenic) Tg2576 mice, various agents which can oppose microglial activation, include vitamin D, genistein, and sesamin. Insulin-degrading enzyme IDE a zinc conserved Zn(2+) metalloprotease can degrade insulin and amylin responsible for the clearance of the cytoplasmic fragment of the amyloid-beta precursor protein (APP) the presence of insulin [IR] signaling will inhibit IDE-mediated degradation of other substances, including beta-amyloid of a variant of the protein TCF7L2 with HHEX and SLC30A8 risk allele gene regions linked to higher risk to develope naturally occurring IDE missense mutations agonists in both diabetes mellitus DM2 and AD therapies for type 2 diabetes leads to an overproduction of Reactive Oxygen Species (ROS) when combined, with each additional risk allele from CDKAL1, and CDKN2A. Repositioning of the IDE domains enables substrate access to the catalytic cavity. IDE interacted with Varicella-zoster virus VZV
glycoprotein E (gE), a protein essential for viral infection,
inhibition or inactivation of a pathogenic mechanism. Insulin-degrading
enzyme (IDE) in neurons and microglia degrades Abeta (APP). Neuron-specific enolase levels were comparable between the AD groups, regardless of the presence or absence APOE status. Both Abeta-synthesizing and -degrading enzyme activities increase with age.

Abeta peptide (APP)-cleaving enzyme (BACE) is a transmembrane aspartyl protease

Alzheimer disease amyloid protein, Amyloid beta A4 protein, Protease nexin-II
The beta-amyloid protein A4 (APP amyloid beta (A4) precursor protein Protease nexin-II ) is derived from a larger protein used for the major protein subunit APP A4 polypeptide Alpha-secretase locus: 21q21: [§§] generates soluble amyloid protein and occurs in the interior. CAA (Cerebral amyloid angiopathy) that results from deposition of beta-amyloid peptide. The study of this disease goes back about hundred years ago to one of the pioneers of the study Oskar Fischer. Neuroserpin (Serpini1) is a neuroprotective component of amyloid plaques, A68 (SERPINA3) may interact with beta A4, ubiquitin involved in protein transport to and from the trans-Golgi network, of endoplasmic reticulum (ER)-associated which may be initiated by insulin-degrading enzyme IDE-generated degradation. Thereby precluding formation and deposition of beta-referred to as beta/A4 and gamma-secretases generated APP components with amyloidogenic features (amyloid plaques, neurofibrillary tangles) progressive cerebral deposition of extracellular filaments the elongation phase of amyloid fibril formation, preventing them from participating in redox cycling with other ligands. Resulting in cell surface delivery of amyloid beta peptide formation and neurotoxicity (AChE) – acetylcholinesterase (Yt blood group) colocalizes with Abeta deposits of brains in AD patients the brain [Brp1] proteoma generation of Abeta involves and accelerates assembly of mutations, homologous to related 5′-UTR of the light and and heavy ferritin genes also the presence of an Iron-Responsive Element (IRE) whereas beta- and gamma-secretases cleave on the N- and C-terminal ends respectively; within Abeta peptide (APP)-cleaving enzyme (BACE) is a transmembrane aspartyl protease* in the brains of transgenic Tg2576 mice in neuritic plaques a high titer of anti-Abeta42 antibodies may protect humans from AD. Some toxic effects are due to other mechanisms (amyloid precursor-like protein-APLP1, A4) as well as in the ultimate apoptotic death localized to multivesicular bodies of neurons at or near the synapse. Processing of APP occurred in the compartment, PLD1 regulates intracellular trafficking, centered within the transmembrane domain transported by kinesin-I. KAI1 was activated by a ternary complex the presenilin-dependent (PSEN1) C-terminal cleavage product that alters proteolytic processing of the synuclein, alpha (non A4 component of amyloid precursor) and amyloid precursor protein (APP) and interactions with X11 proteins APBA1-2 (FE65L1, and FE65L2 amyloid beta (A4) precursor protein-binding, family A, member 1) regulates APP metabolism, dependent on the acetyltransferase activity of TIP60, presenilins (PS1) causal genes are components of gamma-secretase. Nicotine may play an important role in APP secretion and protection against toxicity induced by APP metabolic fragments (beta-amyloid [Abeta], ABAD shows substantial deformation of the active site that prevents nicotinamide adenine dinucleotide (NAD) binding. BACE1 – beta-site APP-cleaving enzyme 1 inhibits in vitro processing of peptide and APP substrates and may be useful for monitoring the effects of drug candidates, A2M – alpha-2-macroglobulin has been implicated biochemically in binding and degradation of the amyloid beta (Abeta) to which alpha-synuclein/NAC precursor, is tightly associated. Phosphorylated C-gamma may accumulate at the splicing factor compartment where ApoEAbeta interaction is critical implications for both Alzheimer’s and prion diseases for progress towards (LRP) low density lipoprotein receptor-related protein that BACE1 can efficiently cleave affects are as a functional linker to pre-mRNA. Splicing is regulated by Fe65 and FE65 a ‘brain-enriched protein’ that binds to APP phosphorylation, fragments are reciprocally involved in the regulation of FE65-dependent gene transactivation not greater than those observed.

Notch1 can trans-activate an APP target gene, Kai1, and vice versa.

    • CD82 molecule, KAI1, Metastasis  suppressor Kangai-1
      CD82 molecule, KAI1, Metastasis suppressor Kangai-1
        • PDB StructureKAI1 was modeled based on crystal structure of the extracellular domain of  tetraspanin  protein member, CD81 1G8Q

          KAI1 cell-surface glycoprotein and the molecular mechanisms underlying the TIP60 coactivator complexes for the metastasis suppressor gene NGF reverts by the expression of the, KAI1: for ‘kang ai‘ ( Chinese for anticancer) locus: 11p11.2; [§§] is a members of the Transmembrane 4 superfamily (TM4SF), are likely to be a selective downregulation strategy for many genes it is an ‘activation antigen’ of T cells at the level of transcription or posttranscription is down-regulated in the progression of common solid epithelial tumors that leads to the down-regulation of the KAI1 gene. KAI1 is the human homolog of the mouse leukocyte surface antigen R2. DARC is essential for the function of CD82 antigen KAI1, CD82 specifically suppresses tumor metastasis of  antigen R2, CD82 (KIA), is incorporated into the viral envelope, gp78 [AMFR-autocrine motility factor receptor] associates with KAI1 (also known as CD82) involved in ER-associated (endoplasmic reticulum) degradation (ERAD), calnexin (CANX) may play a role in this process. Notch1 can trans-activate an APP target gene, Kai1, and vice versa. Tetraspanin-enriched microdomains is important for KAI1/CD82’s motility-inhibitory activity are glycoproteins of unknown function, and is directly associated with the EGF receptor (EGFR). KAI1 was modeled based on crystal structure of the extracellular domain of  tetraspanin  protein member, CD81 and two other tetraspans, CD9-(MRP-1) and CD19. DARC – Duffy blood group, chemokine receptor (Homo sapiens) is essential for the function of CD82, early B cell marker CD9 a molecular partner (CD9P-1) and CD151 (Raph blood group) was found to be coupled. CD151 and CO-029 (TSPAN8 tetraspanin 8) are supposed to promote metastasis formation. KISS1 triggers dormancy in solitary, metastatic tumor cells. COOH-terminal interacting tetraspanin (KITENIN)-vang-like 1 (van gogh, Drosophila) by interacting with KAI1 participates in the regulation of the tumor formation as well as increased invasiveness and cells. Adhesion forces laterally organize cellular membranes via the presence vs absence of, inversely associated univariate and multivariate, Laminin (LN)- or (FN) fibronectin, associations  that usually occur in the context of “tetraspanin web“; its mechanism of action has not yet been fully elucidated.

          Histone acetyltransferase KAT5 Down-regulation and up-stream binding protein LBP1 induces apoptosis via the amyloid beta (A4) precursor-like protein.

          Histone acetyltransferase HTATIP, Histone acetyltransferase KAT5, HIV-1 Tat interactive protein, HTATIP
          Histone acetyltransferase HTATIP, Histone acetyltransferase KAT5, HIV-1 Tat interactive protein, HTATIP
          PDB Structure 2ou2

          Histone acetyltransferase KAT5 also known as Tip60 belongs to the MYST protein family homologous to those of MOZ related to yeast Sas2 locus: 11q13: [§§]. TIP60 represses apoptosis, but also an interaction partner of the Mdm2 oncoprotein , p53 induces (exogenous and endogenous) either cell-cycle, TIP60 on chromatin is decreased following DNA damage after cell death PDCD5 (programmed cell death 5) functions as a Tip60 coactivator and accumulate after exposure to ionizing radiation (IR). A catalytic subunit of the NuA4 histone acetyltransferase complex and a conserved mechanism GCN5 interacts with HTATTIP/TIP60 is a component of the NuA4. Tip60 and HDAC7, interact with each other and repress transcription. A complex formed by Tip60, EPC1, and ING3 is sufficient to reconstitute a trimeric HDAC1 complex as transcriptional repressors in robust nucleosomal HAT (nuclear histone acetyltransferase) activity in vitro the amyloid beta (A4) precursor-like protein 2 (APLP2) induces apoptosis via Tip60 in H4 cells, the general transcription factor TFIID, PCAF complex contains proteins that have histone-like domains. NPAT recruits the TRRAP-Tip60 complex to histone gene promoters. Down-regulation of the tetraspanin KAI1 transcription factor by which phorbol 12-myristate 13-acetate (PMA) up-regulates KAI1, induces recruitment of TIP49 (RuvB-like 1 (E. coli))/Pontin activator complexes to the same motif.

          PCAF-associated factor PAF400


          TRRAP transformation transcription domain-associated protein
          October, 2010
          PDB Structures and Authorized grafitti area 7q21.3-q22.1

          PCAF-associated factor PAF400 is almost identical to TRRAP-PAF is not a protein kinase. TRRAP and GCN5 co-expression stimulated E2F-mediated transactivation. TRRAP is an essential cofactor for both the c-MYC and E1A/E2F oncogenic transcription factor, TIP49 (RuvB-like 1 (E. coli)) to also binds to the E2F1 transactivation domain. The (HAT) complex is responsible for acetylation of the N-terminal tails of histone H3-H4 and H2A homologous (H3K4 trimethylation in vivo requires prior ubiquitination of H2B and the nutrient sensing complex Uri/Prefoldin with TIP49, as a separate biochemically distinct complex ATPase as a cofactor) to human TIP60 (HTATIP) part of a multisubunit NuA4 complex with HAT activity including TRRAP assigned to 7q21.3-q22.1: [§§]. Trrap is, essential for early development and required for maintain mitotic chromatin assembly.

          >KAT2B K(lysine) acetyltransferase 2B, associated with reverse autoacetylation (deacetylation)


          KAT2B K(lysine) acetyltransferase 2B
          PDB Structure Structure and Ligand of a Histone Acetyltransferase Bromodomain
          PDB Structure and Ligand of a Histone Acetyltransferase Bromodomain
          KAT2B K(lysine) acetyltransferase 2B, CBP-associated protein PCAF interact with each other, bind to many sequence-specific factors through a TBP-free TAF-containing-TATA-less promoters complex (called TFTC) and GCN5: [§§] locus: 3p24. In contrast to yeast Gcn5, numerous genes require the histone acetyltransferase (HAT) activities of CBP-associated protein PCAF and the MYST (histone acetyltransferase 1) family members, due to the absence of a Gcn5 homologue (a novel cofactor, ACTR) also demonstrated HAT activity paralogs play roles in the remodeling of chromatin and maintain mitotic H(‘histones’)-K(lysine) chromatin assembly through cell division permits circadian gene expression. MDM2 regulates the stability of PCAF. Poly-ADP-ribose polymerase-2 (PARP-2) is a substrate for the histone, acetyltransferases PCAF and GCN5L, appeared to be the co-repressor protein CtBP an antagonist of the epithelial phenotype and anoikis. p300 HAT was approximately 1000-fold more efficient than PCAF/E1Ap300. CBP/p300, but not P/CAF, enhance EKLF‘s transcriptional activation. Adenovirus E1A protein mimics the effects of Twist with the transformation-transactivation domain-associated protein (TRRAP) involved in the control of cell proliferation, chromatin remodeling and apoptosis-induced stabilization of E2F1 resulted in the acetylation of the PDZ-like domain of SATB1 by PCAF. 2A-DUB (Myb-like, SWIRM and MPN domains 1) interacts with its deubiquitinase activity modulated by the status of (histone deacetylase) HDAC3 (MBD2 could also associate with HDAC2, the promoter becomes absent of HDAC1) associated with reverse autoacetylation (deacetylation) deciphering the epigenetic “code” leads to cytoplasmic accumulation of KAT2B. TBP (TATA-binding protein)-like TFIID, histone fold-containing factors present within the PCAF complex contacting high mobility group (HMG) box binding of Non -istone chromosomal proteins HMG-14 and HMG-17 to nucleosome cores inhibit the hnRNP U, and PCAF complex, protein DEK interacts with mitogen-activated ‘histones’ and exerts a potent inhibitory effect on both p300 and PCAF. Bromodomains recognize p300/CBP-associated factor (PCAF) as acetyl-lysine (Kac) binding of the bromodomain family (bromodomain-containing-BRD1 transcriptional cofactors) also acetylates and activates p53 of an intrinsic HAT activity in BRCA2 irrespective of abolished DNA damage.

          Pol I-specific factor SL1


          SL1 (Transcription initiation factor SL1/TIF-IB subunit C, RNA polymerase I-specific (species-specific)TBP-associated factor 110 kDa mediated TAF(I)110, SL1) is required for RNA polymerase I to synthesize ribosomal RNA of all 3 TAF1 proteins (TAF1A stromelysin-1: [§§], TAF1B: [§§] and TAF1C: [§§]) mutually exclusive binding to TBP excludeing TFIID binding selectivity factor of the RNA polymerase II locus: 1q42, 2p25 and 16q24 termed sulfolipid-1 (TAF1C-SL1). c-Myc and p53 binds to and associates with the Pol I-specific factor SL1 immature dimeric viral RNA palindrome one of the five most frequently mutated TAF(I)68 associated with PCNXL2 and a critical mechanistic link Runx2 complex containing RNA Pol I transcription factors UBF1 and SL1 that affects the rDNA promoter, PCAF acetylates TAF(I)68. The viral human rRNA promoter contains two factor upstream cis-control sequences, the core and upstream control element (UCE), SL1 and SL2 are not functionally equivalent.

          >Upstream binding factor (UBF)


          Upstream binding factor (UBF) locus: 17q21.3: [§§], RNA polymerase I and Pol II-transcribed genes is phosphorylated by casein kinase II (CKII), nucleolar Sirtuin7 (SIRT7) remains associated with the RNA polymerase I (RPI) machinery, and requires at least two auxiliary factors support initiation of SL1 (a complex of TBP) and multiple TBP-associated factors or ‘TAFs’ mediated through several HMG boxes 1 and 2 distributed in several foci during G2 (GRINL1A) than G1 phase nucleolar organizer regions (NORs) leading to a cooperative unfolding of the enhancesome reminiscent of the nucleosome, this nucleolar sequence alone is not sufficient for UBF to accumulate with the processing occurs with utilization of TBP as a component of SL-1 and selectivity factor 1 (SL1) subunit TAFI110 in the nucleolus directs binding to an extended region encompassing sequences in the upstream control element (UCE). UBF1 nucleolar autoantigen (NOR-90) is ninvolved in nucleologenesis distribution of signal recognition particle (SRP) RNA within the nucleolus relates to binding that may be to induce chromatin remodeling, with SL1 and mediates human ribosomal RNA synthesis the histone chaperone B23/nucleophosmin associates with rRNA chromatin (r-chromatin). hPAF49 can interact with activator upstream binding factor (UBF).

          TBP TATA sequence-binding protein-containing complex TFIID

          TBP TATA sequence-binding protein-containing complex TFIID 3 unique subunits (alpha, beta, gamma)
          TBP TATA sequence-binding protein-containing complex TFIID
          PDB Structure 1C9B, 1JFI
          The TBP C-terminal domain locus: 6q27: [§§], is essential for a general master role in the expression of most, if not all, protein-encoding eukaryotic gene b/HLH/Z promoter proximal binding factors expression. And 13 to 14 TBP-associated polypeptide factors known as (TAFs and AF-2 [Furylamide] (formerly TAF-1 and TAF-2 that a subset of TFIID complexes interacts with TAF1, when AF-1 encounters TBP.) identified group of the intrinsically unstructured proteins (IUPs-TBPL1-2 [TATA box binding protein like 1-2], and TRF [TBP-related factor])) the TBP-associated factor TAFII250 the core subunit of TFIID is responsible for promoter recognition TFIIA initiator (Inr)/DNA and resemble each other closely, with the concave face contacting high mobility group (HMG) box HMG1 DNA and the convex interacting, with the D-terminal is the cleft between its two globular domains of basal transcription TBP/TFIID-Inr of a size suitable to bind DNA. The TBP gene consists of impure CAG repeat (SCA17)-induced neurotoxicity. The TATA-box-binding protein TFIID form contacts with a number of retinoblastoma (RB) contacts with a number of viral transactivator proteins. The GATA site can functionally replace the TATA element in the beta-globin promoter from promoters distinct from those of 3 unique subunits (alpha, beta, gamma) known with or without the only known basal factor TATA box TBP recognition element (BRE) is specific to this complex, the initiator (INR) and the downstream promoter element (DPE). The SWI/SNF chromatin-remodeling complex that modifies the nucleosome to allow binding of TBP, the Negative co-factor 2 (NC2) regulates the preinitiation (PIC) complex. Dr1 (- down-regulator of transcription 1, TBP) affected its interaction as it can be condensed into transcriptionally silent chromosomes consistent with TBP-containing complex TFIIIB-related factor, BRF from U6 (RNA U6A,B&C small nuclear), a different variant hBRF2 is required at the human U6 promoter of a RNA polymerase III is composed of 16 subunits and reqiures the snRNA-activating protein complex (SNAP(c)) which consists of five types of subunits for TBP function at U6 promoters, and 7SK promoters in the absence of DNA for transcription of low affinities (USF the b/HLH/Z promoter can interact with TFIID to effect activation) and kinetics in binding to the various protein TATA-less RNA polymerase III genes of human RNA Pol III transcription initiation factor IIIB and promoter element 2 with activators to increase transcription by the RNA PolII. Dr1 may shift the physiological balance of transcriptional output in favor of polymerase I. SL1 [TATA box binding protein (TBP)-associated factor, RNA polymerase I requires two transcription factors, upstream binding factor (UBF) and promoter selectivity factor (SL1)] and D-TFIID are involved in RNA polymerase I and II transcription from the TATA-containing U6 promoter. SDHA were the most stable the (YWHAZ) dimer promotes homodimerization and heterodimerization with YWHAE for their expression stability housekeeping gene and TBP level in placental mRNA.

          The role of TFII-I outside the nucleus an E box element on Spin visual spatial functioning.

          Il Dr.Psycho dice che sono:stupido(ma non è colpa mia)Scopri cosa dice di te su

          About PsycHo generated via PsycHo

          LE MODERNISTE - Restricted Thinking This cd-r is built around mental disorder and the therapeutics, especially Electro Convulsive Therapy and transorbital lobotomy Dr. psycho, stupido. Cell corpse regulon
          entities making repeated determination useless, proposed for this ZMPSTE24 (- zinc metallopeptidase (STE24 homolog, S....of accelerated ageing syndromes)

          ZBTB24 Mutation of the outer sphere solvent pocket residue iron-substituted Q146 has a more dramatic (X)

          Within GTF2I general transcription 2, I-(MusTRD1), bind to similar but distinct sequences, is BAP135 a downstream target of BTK, a protein they designated BAP135 Bruton tyrosine kinase-associated protein locus: 7q11.23 [§§], which possesses a potential helix-loop/span-helix motif or a partial (WBS) deletion of band 7q11.23. GTF2I and USF1 can also act synergistically formed both homomeric and heteromeric interactions found inside the nucleus transactivation of reporter genes heat shock protein 5, GRP78/BiP . One of the E-box motifs overlaps the cis-regulatory DNA TATA and/or initiator (Inr) and this interacts with USF1 and TFII-I in vitro at the upstream RBEIII element that RBF-2 is comprised of. The role of TFII-I outside the nucleus, suppresses calcium entry by competing with TRPC3 for binding to agonist-induced PLC-gamma. TFII-I and/or factors that binds specifically to Inr elements to three regulatory E boxes in the human VEGFR-2 kinase insert domain receptor VEGFR-2/KDR/flk-1 (a type III receptor tyrosine kinase) promoter, contribute to the efficient formation of transcription complexes on the adult beta-globin gene and TFII-I (contribute to (WBS) deficits on visual spatial functioning), which bind’s to the X mutation brain-specific Zbtb24; cooperatively this overlap interacts less efficiently than it (USF1/USF2) binds to an E box element.

          USF2 (upstream stimulatory factors) interact cooperatively upstream elements USF2 up-regulate from the first exon over this gene

          The basic/helix-loop-helix/leucine zipper (b/HLH/Z) transcription factor upstream stimulatory factor (USF)
          The basic/helix-loop-helix/leucine zipper (b/HLH/Z) transcription factor upstream stimulatory factor (USF)
          USF1 and USF2 (upstream stimulatory factor) are basic helix-loop-helix transcription factors USF2 or known as FIP, locus: 19q13 [§§], contained both 10 exons from the first exon over this gene in intron 1 a third element, F which contains an E-box, an activation domain (heterodimer) and a negative regulatory region (homodimer). USF2 binding a fragment of DNA and TFII-I interact cooperatively at the upstream RBEIII element containing three E boxes. USF2 decreased binding of endogenous (upstream stimulatory factor) USF to the E-box element located in the organic cation transporter OCT1 core capable of activating a negative effect on the cell proliferation in some cell types mediates glucose-induced thrombospondin 1 (TSP1) expression but the interaction comprised TFII-I for repression of viral expression, which bind cooperatively to RBEIII binds the factor RBF-2, is stimulated by TFII-I interact cooperatively at the upstream RBEIII element. USF2 up-regulate gene expression (i.e., HIV-1 long terminal repeats) via interaction with an E box Adenovirus-mediated overexpression of USF2 decreased binding of endogenous USF, exogenous USF2 repressed activation of the TERT promoter and suppress human upstream stimulatory factors promoter/enhancer activity showed an enrichment of IGFBP3 promoter in insulin-treated cells this hormone is found in the cytoplasm. (PPAR) pathway PGC-1 and USF2 proteins can physically interact.

          Hepcidin antimicrobial peptideHepcidin antimicrobial peptide (HAMP) locus: 19q13 [§§], is a 25aa-amino-acid antimicrobial peptide systemic iron homeostasis depends on by a furin-dependent process, that disrupt the cell membranes of cellular pathogens. HAMP is most active against gram-positive bacteria also certain yeast and gram-negative species formed by the defensins as a subfamily of antimicrobially active peptides of animals and plants. TMPRSS6 as an essential component of a pathway that detects iron deficiency by controlling HAMP absorption and its upstream, USF2 gene. SLC40A1/ferroportin destroyed by interaction with the (HAMP) peptide, SLC40A1 is the only known transporter that facilitates iron egress.

          Liver iron transport expression and the expression of hepcidin.

          Hemochromatosis type 2B-HFE2 (JHV) locus: 1q21 [§§] is caused by mutation in the (HAMP) hepcidin gene, hemojuvelin disrupt transferrin-bound irons ability to stimulate expression and may influence the phenotype with adult-onset HFE hemochromatosis in the state of JH (heavychaindiversity joining region (JH) immunoglobulin gene) even at a young age, mainly due to chromosome 1q-linked juvenile hemochromatosis. Hemojuvelin acts through the multifunctional (BMP) bone morphogenetic protein pathway and neogenin that regulates hepcidin expression and bind simultaneously. Hemojuvelin is a member of the repulsive guidance molecule (RGM) family controlled by the liver-derived peptide hepcidin mediated by the transporter DMT1 (SLC11A1) reduced by the ferric CYBRD1 cytochrome b reductase Dcytb, which display very low expression of liver hepcidin essential to maintain body iron homeostasis. Iron that is not specifically chaperoned through its essential functional pathways is damaging to biological systems.

          Human ferritins

          Ferritin Light Chain
          Structure of Human Ferritin L Chain
          A hollow sphere that permits entry of a variable amount of iron for storage as ferric hydroxide phosphate complexes. 2FG4
          Human ferritins are a hollow sphere that permits entry of ferric hydroxide phosphate complexes into a hollow cavity to bind at the ferroxidase center (FERROPORTIN~ 1ZJ8). The H and L subunits are not functionally interchangeable, Ferritin Light Chain locus: 19q13.3-q13.4 [§§] have different mRNA molecules the heavy subunit (rich in human heart ferritin) is located on chromosome 11. These mutations are responsible for the diseases hereditary haemochromatosis (HFE) (autosomal recessive) and Hyperferritinemia syndrome are light-diffracting ferritin crystals. Iron chaperones poly(rC) binding protein-1 (PCBP1) are needed for delivery of iron to ferritin. In plant cells it is found in chloroplasts and other plastids.

          Hepcidin antimicrobial peptide with ferroportin (FPN)

          Hepcidin antimicrobial peptide with ferroportin (FPN)

          SLC40A1 solute carrier family 40 (iron-regulated transporter), member 1 Ferroportin-1, locus: 2q32 [§§] is mediated by the divalent metal transporter, DMT1 and the duodenal iron transporters divalent-metal transporter 1 (SLC11A1). Hemochromatosis genes encode molecules that regulate hepcidin synthesis described for C282Y mutations or TFR2 (transferrin receptor 2) of genes controlling iron metabolism, and two CYBRD1 gene mutations. Hepcidin antimicrobial peptide directly interacts with ferroportin (FPN) and modulates iron transport from macrophages and enterocytes to red blood cell precursors. Ferroportin-1 (SLC11A3) is involved in iron export from enterocytes in mammals, initiated by uptake of ferrous Fe(II) iron across the brush border membrane and localized to the basolateral membrane requires: a glycophosphosinositide-linked, CP gene found in ceruloplasmin and its homologue copper-containing iron oxidase known as (Heph) hephaestin. A mutation in the SLC40A1 genes (Ferroportin) secondary effects of the ‘erythropoietic regulator’ stimulating intestinal iron absorption from dietary sources, and point mutation in the L ferritin (FTL; 134790) in lens ferritin accumulation contributing to age-related cataract in situations that alter normal iron homeostasis of certain forms of “ferroportin disease” results from dominant negative effects either a regulatory function or as the necessary link in iron homeostasis in health and disease can be interpreted.