192258 Results for: "Magnesium+tert-butoxide&pageNo=50&view=easy"

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Transcription factor required for formation of positional identity in the developing retina, regionalization of the optic chiasm and morphogenesis of the kidney. Can neuralize ectodermal cells directly By similarity. Binds to the consensus sequence 5'-A[AT]T[AG]TTTGTTT-3' and acts as a transcriptional repressor. Also acts as a transcriptional activator. Promotes development of neural crest cells from neural tube progenitors. Restricts neural progenitor cells to the neural crest lineage while suppressing interneuron differentiation. Required for maintenance of pluripotent cells in the pre-implantation and peri-implantation stages of embryogenesis. Probable transcription factor involved in embryogenesis and somatogenesis. FOXD1 is involved in regulating inflammation as well as kidney and retinal development. FOXD1 regulates the activity of NFAT and NFkB. Deficiency of FOXD1 results in multiorgan systemic inflammation, exaggerated Th cell-derived cytokine production, and T cell proliferation in autogolgous MLRs. In kidneys, FOXD1 controls the production of signals required for the normal transition of induced mesenchyme into tubular epithelium and full growth and branching of the collecting system. Deletion of FOXD1 results in renal abnormalities. FOXD2 acts as a modulator of T cell activation.

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The sense of taste provides animals with valuable information about the quality and nutritional value of food. A family of G protein-coupled receptors are involved in taste perception and include T1R, which is involved in sweet and umami taste perception, and T2R, which is involved in bitter taste perception. Both types of taste receptors couple to various G proteins to initiate signal transduction cascades. Single taste receptor cells express a variety of T2Rs, suggesting that each cell is capable of recognizing multiple tastants. T2R6 (also designatedT2R30, mt2r42, STC 7-4 or taste receptor, type 2, member 130) is an integral membrane receptor protein in mice that may play a role in the perception of bitterness and in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate Alpha-gustducin, mediate PLC-Beta-2 activation and lead to the gating of TRPM5. T2R6 is expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells. The human homolog of T2R6, designated T2R7 (TAS2R7, TRB4 or taste receptor, type 2, member 7) is a G protein-coupled receptor expressed in taste receptor cells of the tongue and palate epithelia.

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Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by loss of motor neurons in the spinal cord. SMA is caused by deletion or loss-of-function mutations in the SMN (survival of motor neuron) gene. Gemin2 (formerly known as SIP1 for SMN interacting protein) associates directly with SMN and is a part of the SMN complex containing Gemin3 (a DEAD-box RNA helicase), Gemin4, Gemin5 and Gemin6, as well as several spliceosomal snRNP proteins. The SMN complex plays an essential role in splicesomal snRNP assembly in the cytoplasm and is required for pre-mRNA splicing of the nucleus. It is found in both the cytoplasm and the nucleus. The nuclear form is concentrated in subnuclear bodies called gems (Gemini of the coiled bodies). The SMN-Gemin2 complex is associated with spliceosomal snRNAs U1 and U5. Gemin2 is expressed in spinal cord. It can be induced by TGF∫ treatment and expression is high in several E-cadherin negative human carcinoma cell lines. SMN is expressed in a wide variety of tissues including brain, kidney, liver and spinal cord, and moderately in skeletal and cardiac muscle. The gene encoding Gemin2 maps to human chromosome 14q13.

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Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by loss of motor neurons in the spinal cord. SMA is caused by deletion or loss-of-function mutations in the SMN (survival of motor neuron) gene. Gemin2 (formerly known as SIP1 for SMN interacting protein) associates directly with SMN and is a part of the SMN complex containing Gemin3 (a DEAD-box RNA helicase), Gemin4, Gemin5 and Gemin6, as well as several spliceosomal snRNP proteins. The SMN complex plays an essential role in splicesomal snRNP assembly in the cytoplasm and is required for pre-mRNA splicing of the nucleus. It is found in both the cytoplasm and the nucleus. The nuclear form is concentrated in subnuclear bodies called gems (Gemini of the coiled bodies). The SMN-Gemin2 complex is associated with spliceosomal snRNAs U1 and U5. Gemin2 is expressed in spinal cord. It can be induced by TGF∫ treatment and expression is high in several E-cadherin negative human carcinoma cell lines. SMN is expressed in a wide variety of tissues including brain, kidney, liver and spinal cord, and moderately in skeletal and cardiac muscle. The gene encoding Gemin2 maps to human chromosome 14q13.

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Chk2 is a serine/threonine kinase involved in the control of cell cycle checkpoints, and may also participate in transduction of the DNA damage and replicational stress signals. Chk2 is the mammalian ortholog of the budding yeast Rad53 and fission yeast Cds1 checkpoint kinases. The amino-terminal domain of Chk2 contains a series of seven serine and threonine residues (Ser19, Thr26, Ser28, Ser33, Ser35, Ser50 and Thr68) followed by glutamine (SQ or TQ motif). These are known to be preferred sites for phosphorylation by ATM/ATR kinases. Indeed, after DNA damage by ionizing radiation (IR), UV irradiation or hydroxyurea treatment, Thr68 and other sites in this region become phosphorylated by ATM/ATR. The SQ/TQ cluster domain, therefore, seems to have a regulatory function. Phosphorylation at Thr68 is a prerequisite for the subsequent activation step, which is attributable to autophosphorylation of Chk2 on residues Thr383 and Thr387 in the activation loop of the kinase domain. Chk2 inhibits CDC25C phosphatase by phosphorylating it on Ser-216, preventing the entry into mitosis. This kinase may have a role in meiosis as well. Kinase activity is up regulated by autophosphorylation and the protein is rapidly phosphorylated in response to DNA damage and to replication block.

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Members of the GATA family share a conserved zinc finger DNA-binding domain and are capable of binding the WGATAR consensus sequence. GATA-1 is erythroid-specific and is responsible for the regulated transcription of erythroid genes. It is an essential component in the generation of the erythroid lineage. GATA-2 is expressed in embryonic brain and liver, HeLa and endothelial cells, as well as in erythroid cells. Studies with a modified GATA consensus sequence, AGATCTTA, have shown that GATA-2 and GATA-3 recognize this mutated consensus while GATA-1 has poor recognition of this sequence. This indicates broader regulatory capabilities of GATA-2 and GATA-3 than GATA-1. GATA-3 is highly expressed in T lymphocytes. GATA-4, GATA-5 and GATA-6 comprise a subfamily of transcription factors. Both GATA-4 and GATA-6 are found in heart, pancreas and ovary; lung and liver tissues exhibit GATA-6, but not GATA-4 expression. GATA-5 expression has been observed in differentiated heart and gut tissues and is present throughout the course of development in the heart. Although expression patterns of the various GATA transcription factors may overlap, it is not yet apparent how the GATA factors are able to discriminate in binding their appropriate target sites.

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Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.

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ATF2 is a member of the ATF/CREB family of basic region leucine zipper DNA binding proteins that regulates transcription by binding to a consensus cAMP response element (CRE) in the promoter of various viral and cellular genes. Many of these genes are important in cell growth and differentiation, and in stress and immune responses. ATF2 is a nuclear protein that binds DNA as a dimer and can form dimers with members of the ATF/CREB and Jun/Fos families. It is a stronger activator as a heterodimer with cJun than as a homodimer. Several isoforms of ATF2 arise by differential splicing. The stable native full length ATF2 is transcriptionally inactive as a result of an inhibitory direct intramolecular interaction of its carboxy terminal DNA binding domain with the amino terminal transactivation domain. Following dimerization ATF2 becomes a short lived protein that undergoes ubiquitination and proteolysis, seemingly in a protein phosphatase-dependent mechanism. Stimulation of the transcriptional activity of ATF2 occurs following cellular stress induced by several genotoxic agents, inflammatory cytokines, and UV irradiation. This activation requires phosphorylation of two threonine residues in ATF2 by both JNK/SAP kinase and p38 MAP kinase. ATF2 is abundantly expressed in brain.

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The activation of RaP1 by cAMP is independent of PKA and is mediated by recently discovered family of guanine nucleotide exchange factors (GEFs) called cAMP-GEFs or Epacs. The Epac signaling therefore represents a novel mechanism for cAMP signaling with in the cAMP cascade. There are 2 members of the Epac family, Epac1 and Epac 2. Both proteins are multidomain proteins containing an autoinhibitory cAMP-binding domain that inhibits the catalytic region and a DEP domain (dishevelled, Egl-10 and pleckstrin homology domain) targeting the membrane anchors. EPAC2 has an additional cAMP-binding site in its N-terminus that binds cAMP with low affinity. EPAC1 mRNA is broadly expressed, with particularly high levels occurring in the thyroid, ovary, kidney and certain brain regions, whereas expression of EPAC2 mRNA appears to be restricted to the brain and adrenal glands. Epac 1 and Epac 2 also interact with light chain 2 (LC2) or MAP1A that serves as a scaffolding structure to stabilize the signal transduction complex. The Epac 1-selective were generated against unique antigenic sequences form near N-terminus and between RasGEFN and Ras GEF domains. The to Epac 1are affinity purified over immobilized antigen based chromatography.

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Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3'). In the nucleus, contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. In the cytoplasm, interacts with and perturbs HK1- and VDAC1-containing complexes at the mitochondrial outer membrane, thereby impairing mitochondrial membrane potential, inducing mitochondrial leakage and promoting cell death. The phosphorylated form (mediated by ATM) plays a role in the DNA damage response and is involved in the ionizing radiation (IR)-induced S phase checkpoint control and in the recruitment of the MRN complex into the IR-induced foci (IRIF). Exhibits histone acetyltransferase (HAT) activity which specifically acetylates histones H2B and H4 in vitro. In concert with CUL3 and RBX1, promotes the degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Can elicit oncogenic or tumor suppressor activities depending on the tissue or cell type.

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ATF2 is a member of the ATF/CREB family of basic region leucine zipper DNA binding proteins that regulates transcription by binding to a consensus cAMP response element (CRE) in the promoter of various viral and cellular genes. Many of these genes are important in cell growth and differentiation, and in stress and immune responses. ATF2 is a nuclear protein that binds DNA as a dimer and can form dimers with members of the ATF/CREB and Jun/Fos families. It is a stronger activator as a heterodimer with cJun than as a homodimer. Several isoforms of ATF2 arise by differential splicing. The stable native full length ATF2 is transcriptionally inactive as a result of an inhibitory direct intramolecular interaction of its carboxy terminal DNA binding domain with the amino terminal transactivation domain. Following dimerization ATF2 becomes a short lived protein that undergoes ubiquitination and proteolysis, seemingly in a protein phosphatase-dependent mechanism. Stimulation of the transcriptional activity of ATF2 occurs following cellular stress induced by several genotoxic agents, inflammatory cytokines, and UV irradiation. This activation requires phosphorylation of two threonine residues in ATF2 by both JNK/SAP kinase and p38 MAP kinase. ATF2 is abundantly expressed in brain.

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PDZRN3 contains a RING-finger motif in its N-terminal region, two PDZ domains in its central region and a consensus-binding motif for PDZ domains at its C-terminus. It was identified in silico as a homolog of the protein known as LNX1 or SEMCAP1, which possesses ubiquitin ligase activity and binds the membrane protein Semaphorin 4C. However, PDZRN3 itself has not previously been characterized. We have now evaluated the properties and functions of PDZRN3. The PDZRN3 gene was shown to be expressed in various human tissues including the heart, skeletal muscle and liver and its expression in mouse skeletal muscle was developmentally regulated. Both the differentiation of C2C12 mouse skeletal myoblasts into myotubes and injury-induced muscle regeneration in vivo were found to be accompanied by up-regulation of PDZRN3. The differentiation-associated increase in the expression of PDZRN3 in C2C12 cells follows that of myogenin and precedes that of myosin heavy chain. Depletion of PDZRN3 by RNA interference inhibited the formation of myotubes as well as the associated up-regulation of myosin heavy chain in C2C12 cells. Our data suggest that PDZRN3 plays an essential role in the differentiation of myoblasts into myotubes by acting either downstream or independently of myogenin.

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Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity. As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival. May contribute to caspase inhibition, by blocking the ability of DIABLO/SMAC to disrupt XIAP/BIRC4-caspase interactions. Protects against apoptosis induced by TNF or by chemical agents such as adriamycin, etoposide or staurosporine. Suppression of apoptosis is mediated by activation of MAPK8/JNK1, and possibly also of MAPK9/JNK2. This activation depends on TAB1 and NR2C2/TAK1. In vitro, inhibits CASP3 and proteolytic activation of pro-CASP9. Isoform 1 blocks staurosporine-induced apoptosis. Isoform 2 blocks etoposide-induced apoptosis. Isoform 2 protects against natural killer (NK) cell killing whereas isoform 1 augments killing.

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Transcriptional coactivator of the p300/CBP-mediated trancription complex. Acts as a bridge, linking TFAP2 transcription factors and the p300/CBP transcriptional coactivator complex in order to stimulate TFAP2-mediated transcriptional activation. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Stimulates the peroxisome proliferator-activated receptors PPARA transcriptional activity. Enhances estrogen-dependent transactivation mediated by estrogen receptors. Acts also as a transcriptional corepressor; interferes with the binding of the transcription factors HIF1A or STAT2 and the p300/CBP transcriptional coactivator complex. Participates in sex determination and early gonad development by stimulating transcription activation of SRY. Plays a role in controlling left-right patterning during embryogenesis; potentiates transcriptional activation of NODAL-mediated gene transcription in the left lateral plate mesoderm (LPM). Plays an essential role in differentiation of the adrenal cortex from the adrenogonadal primordium (AGP); stimulates WT1-mediated transcription activation thereby up-regulating the nuclear hormone receptor NR5A1 promoter activity. Associates with chromatin to the PITX2 P1 promoter region.

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CPXM (carboxypeptidase X, member 1) belongs to the peptidase M14 family. However, no carboxypeptidase activity has yet been detected. It may be involved in cell-cell interactions.Members of the M14 metallocarboxypeptidase protein family serve many diverse functions and are divided into three subfamilies based on structure, function and amino acid sequence similarity. Belonging to the N/E subfamily, CPXM (metallocarboxypeptidase CPX-1) is a 734 amino acid protein that contains a F5/8 type C domain and likely binds one zinc ion per subunit. Most members of the N/E subfamily contain several domains, including an active carboxypeptidase domain and signal peptide, and are thought to function mostly in protein-protein interactions and/or protein-membrane interactions, thereby targeting the protein to specific locations within the secretory pathway. CPXM is a unique member of this subfamily in that it does not appear to exhibit any enzymatic activity due to lack of several active-site residues that are present in the catalytic domain of other members of the N/E subfamily. Studies showing that CPXM expression is regulated during osteoclastogenesis suggest that CPXM may play a role in osteoclast differentiation. There are two isoforms of CPXM which are a result of alternative splicing events.

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Microtubule-associated proteins (MAPs) regulate microtubule stability and play critical roles in neuronal development and in maintaining the balance between neuronal plasticity and rigidity. MAP-light chain 3 beta (MAP-LC3 Beta) and MAP-light chain 3 alpha (MAP-LC3 alpha) are subunits of both MAP1A and MAP1B. MAP-LC3M Beta, a homolog of Apg8p, is essential for autophagy and associated to the autophagosome membranes after processing. Two forms of LC3 Beta, the cytosolic LC3-I and the membrane-bound LC3-II, are produced post-translationally. LC3-I is formed by the removal of the C-terminal 22 amino acids from newly synthesized LC3∫, followed by the conversion of a fraction of LC3-I into LC3-II. LC3 enhances fibronectin mRNA translation in ductus arteriosus cells through association with 60S ribosomes and binding to an AU-rich element in the 3’ untranslated region of fibronectin mRNA. This facilitates sorting of fibronectin mRNA onto rough endoplasmic reticulum and translation. MAP LC3 Beta may also be involved in formation of autophagosomal vacuoles. It is expressed primarily in heart, testis, brain and skeletal muscle.

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Cytokeratins, a group comprising at least 29 different proteins, are characteristic of epithelial and trichocytic cells. Cytokeratins 1, 4, 5, 6, and 8 are members of the type II neutral to basic subfamily. Antibody to cytokeratins are specific markers of epithelial cell differentiation and have been widely used as tools in tumor identification and classification. Anti Pan Cytokeratin (mixture) is a broadly reactive reagent, which recognizes epitopes present in most human epithelial tissues. It facilitates typing of normal, metaplastic and neoplastic cells. Synergy between the various components results in staining amplification. This enables identification of cells, which would otherwise be stained only marginally. The mixture may aid in the discrimination of carcinomas and nonepithelial tumors such as sarcomas, lymphomas and neural tumors. It is also useful in detecting micrometastases in lymph nodes, bone marrow and other tissues and for determining the origin of poorly differentiated tumors. There are two types of cytokeratins the acidic type I cytokeratins and the basic or neutral type II cytokeratins. Cytokeratins are usually found in pairs comprising a type I cytokeratin and a type II cytokeratin. Usually the type II cytokeratins are 8kD larger than their type I counterparts.

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Serotonin (also designated 5-hydroxytryptamine or 5-HT) is a molecule that functions as a neurotransmitter, a hormone and a mitogen, and it is predominantly expressed in the gut, platelets and central nervous system (CNS). In the CNS, serotonin modulates several processes, including anxiety, sleep, appetite, behavior and drug abuse. In platelets and gut, serotonin plays a major role in cardiovascular function and motility of the gastrointestinal tract, respectively. Serotonin mediates its effects through several of G protein coupled receptors, designated 5-HT receptors or alternatively SR receptors. The SR-2 receptors are comprised of three subtypes, SR-2A, SR-2B and SR-2C, which activate phospholipase C and release intracellular stores of calcium in response to serotonin. SR-2A has a specific role in tracheal smooth muscle contraction, bronchoconstriction and mediating aldosterone production, and it is also thought to play a role in several psychiatric disorders, including depression and schizophrenia. SR-2B is expressed in embryonic and adult cardiovascular tissues, gut and brain and plays an important role in the pathology of cardiac disorders. SR-2C is thought to mediate the effects of atypical antipsychotic drugs.

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Rabphilin-3AL (rabphilin-3A-like), also known as RPH3AL or NOC2, is a cytoplasmic Rab GTPase effector. It contains one FYVE-type zinc finger and one Rab-binding (RBD) domain, but unlike its related protein, rabphilin-3A, rabphilin-3AL does not contain any C2 domains. Rabphilin-3AL is expressed in a variety of tissues, with highest levels found in kidney, skeletal muscle, pancreas, liver, ovary, stomach, heart and thyroid. It is believed to play a role regulating calcium-dependent secretory vesicle exocytosis in endocrine and exocrine cells. Via its RBD domain, rabphilin-3AL is capable of binding Rab 27a and, through this interaction, rabphilin-3AL is recruited to dense-core vesicles. With lower affinity, rabphilin-3AL can also bind Rab 3 and Rab 8 with its RBD domain. Through an interaction with Rab 3, rabphilin-3AL can inhibit G-protein signaling in endocrine pancreas and positively regulate insulin secretion. Rabphilin-3AL knockout mice display accumulation of secretory granules and irregular shape in exocrine cells.

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Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.

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Caspases are a family of intracellular proteases that mediate cell death and are the principal effectors of apoptosis. Caspase 10 (Mch4, ICE-LAP4, FLICE2) plays an important role in apoptosis induced by a variety of inducers such as TNF alpha and Anti-Fas antibody. It is a large prodomain caspase classified together with caspases 2, 8, and 9 as a signaling caspase. Four isoforms of caspase 10 (caspase 10a, 10b, 10c, and 10d) having the same prodomain but different mature large and small subdomain, have been described. Caspase 10 contains two death domains (DED) involved in linking to the death effector domain of the adapter protein FADD and recruiting the complex to TNFR1 and Fas. The inactive procaspase 10 is variably expressed in many tissues and cell lines as a cytosolic protein. The mature form of caspase 10 comprises two subunits, p23/p17 (splice isoforms) and p12. Interestingly, a caspase 9- dependent processing of caspase 10 by caspase 6 in cell-free extracts has recently been suggested. Caspase 10 can cleave and activate caspases 3, 4, 6, 7, 8, and 9. This is followed by cleavage of numerous key proteins, including the nuclear protein PARP.

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Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TENC1. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. In case of filovirus infection, seems to function as a cell entry factor.

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CCDC17, also known as FLJ17921 or RP4-697E16.4, is a 622 amino acid protein expressed as four isoforms and encoded by a gene mapping to human chromosome 1. Chromosome 1 is the largest human chromosome spanning about 260 million base pairs and making up 8% of the human genome. There are about 3,000 genes on chromosome 1, and considering the great number of genes there are also a large number of diseases associated with chromosome 1. Notably, the rare aging disease Hutchinson-Gilford progeria is associated with the LMNA gene which encodes lamin A. When defective, the LMNA gene product can build up in the nucleus and cause characteristic nuclear blebs. The mechanism of rapidly enhanced aging is unclear and is a topic of continuing exploration. The MUTYH gene is located on chromosome 1 and is partially responsible for familial adenomatous polyposis. Stickler syndrome, Parkinsons, Gaucher disease and Usher syndrome are also associated with chromosome 1. A breakpoint has been identified in 1q which disrupts the DISC1 gene and is linked to schizophrenia. Aberrations in chromosome 1 are found in a variety of cancers including head and neck cancer, malignant melanoma and multiple myeloma.

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Uteroglobin belongs to the family of secretoglobins and is a secreted protein product of nonciliated bronchiolar Clara cells. There is convincing data suggesting it has phospholipase A2 inhibitory activity, as well as, a number of other immunomodulatory features including inhibition of interferon gamma signalling and Th1 vs. Th2 lymphocyte regulation. It was proposed as a potential peripheral marker of respiratory epithelial injury and bronchial dysfunction. Clara Cell Protein 16 concentrations have been determined in both serum and bronchoalveolar lavage fluid in numerous studies since 1994. In serum, its increase is associated with age, asbestos, nitrogen chloride and ozone exposure, sarcoidosis and high PEEP ventilation. Decreased serum CC16 levels are found after pulmonary resection, in silica-exposed workers, smokers and in asthma. Decreased CC16 concentrations were also found in the amniotic fluid of fetuses suffering from pulmonary hypoplasia caused by various mechanisms (diaphragmatic hernia, diabetic fetopathy, Turner and Down syndrome). In pleural effusions, the CC16 concentration appears to be associated with its diffusion from the lung as evidenced by high CC16 levels in cardiac pleural congestion.

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Plays a major role in the induction and maintenance of cellular transformation. Acts mainly as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. E6 associates with host E6-AP ubiquitin-protein ligase, and inactivates tumor suppressors TP53 and TP73 by targeting them to the 26S proteasome for degradation. In turn, DNA damage and chromosomal instabilities increase and lead to cell proliferation and cancer development. The complex E6/E6P targets several other substrates to degradation via the proteasome including host NFX1-91, a repressor of human telomerase reverse transcriptase (hTERT). The resulting increased expression of hTERT prevents the shortening of telomere length leading to cell immortalization. Other cellular targets including Bak, Fas-associated death domain-containing protein (FADD) and procaspase 8, are degraded by E6/E6AP causing inhibition of apoptosis. E6 also inhibits immune response by interacting with host IRF3 and TYK2. These interactions prevent IRF3 transcriptional activities and inhibit TYK2-mediated JAK-STAT activation by interferon alpha resulting in inhibition of the interferon signaling pathway.

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The mitotic checkpoint ensures that chromosomes are divided equally between daughter cells and is a primary mechanism preventing the chromosome instability often seen in aneuploid human tumors. This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. The encoded protein binds to centromeres during the prophase, metaphase, and early anaphase cell division stages and to kinetochore microtubules during metaphase. It is part of the MIS12 complex, which may be fundamental for kinetochore formation and proper chromosome segregation during mitosis. In mitotic human cells ZW10 resides in a complex with Rod and Zwilch, whereas another ZW10 partner, Zwint-1, is part of a separate complex of structural kinetochore components including Mis12 and Ndc80-Hec1. Zwint-1 is critical for recruiting ZW10 to unattached kinetochores. Depletion from human cells demonstrates that the ZW10 complex is essential for stable binding of a Mad1-Mad2 complex to unattached kinetochores. Thus, ZW10 functions as a linker between the core structural elements of the outer kinetochore and components that catalyze generation of the mitotic checkpoint-derived "stop anaphase" inhibitor.

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Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.

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Members of the GATA family share a conserved zinc finger DNA-binding domain and are capable of binding the WGATAR consensus sequence. GATA-1 is erythroid-specific and is responsible for the regulated transcription of erythroid genes. It is an essential component in the generation of the erythroid lineage. GATA-2 is expressed in embryonic brain and liver, HeLa and endothelial cells, as well as in erythroid cells. Studies with a modified GATA consensus sequence, AGATCTTA, have shown that GATA-2 and GATA-3 recognize this mutated consensus while GATA-1 has poor recognition of this sequence. This indicates broader regulatory capabilities of GATA-2 and GATA-3 than GATA-1. GATA-3 is highly expressed in T lymphocytes. GATA-4, GATA-5 and GATA-6 comprise a subfamily of transcription factors. Both GATA-4 and GATA-6 are found in heart, pancreas and ovary; lung and liver tissues exhibit GATA-6, but not GATA-4 expression. GATA-5 expression has been observed in differentiated heart and gut tissues and is present throughout the course of development in the heart. Although expression patterns of the various GATA transcription factors may overlap, it is not yet apparent how the GATA factors are able to discriminate in binding their appropriate target sites.

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Plays a major role in the induction and maintenance of cellular transformation. Acts mainly as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. E6 associates with host E6-AP ubiquitin-protein ligase, and inactivates tumor suppressors TP53 and TP73 by targeting them to the 26S proteasome for degradation. In turn, DNA damage and chromosomal instabilities increase and lead to cell proliferation and cancer development. The complex E6/E6P targets several other substrates to degradation via the proteasome including host NFX1-91, a repressor of human telomerase reverse transcriptase (hTERT). The resulting increased expression of hTERT prevents the shortening of telomere length leading to cell immortalization. Other cellular targets including Bak, Fas-associated death domain-containing protein (FADD) and procaspase 8, are degraded by E6/E6AP causing inhibition of apoptosis. E6 also inhibits immune response by interacting with host IRF3 and TYK2. These interactions prevent IRF3 transcriptional activities and inhibit TYK2-mediated JAK-STAT activation by interferon alpha resulting in inhibition of the interferon signaling pathway.

Supplier: Bioss

The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the `pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. The function of the ataxins is not known. This locus has been mapped to chromosome 6, and it has been determined that the diseased allele contains41-81 CAG repeats, compared to 6-39 in the normal allele, and is associated with spinocerebellar ataxia type 1 (SCA1). At least two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq].