Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antimicrobial, immunomodulatory, and cell growth-regulatory activities of the interferons are mediated by interferon-inducible proteins. One of these is p202, a nuclear protein that is encoded by the Ifi 202 gene from the interferon-activatable gene 200 cluster. Overexpression of p202 in transfected cells slows down cell proliferation. As shown earlier, p202 binds to the hypophosphorylated form of the retinoblastoma susceptibility protein. Here we report that p202 inhibits the activities of the NF-kappa B and the AP-1 enhancers both in transiently transfected cells and in transfected stable cell lines overexpressing p202. Furthermore, p202 binds the NF-kappa B p50 and p65 and the AP-1 c-Fos and c-Jun transcription factors in vitro and in vivo. NF-kappa B, c-Fos, and c-Jun participate in the transcription of various cellular and viral genes, and thus p202 can modulate the expression of these genes in response to interferons.
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PMID:The interferon-inducible p202 protein as a modulator of transcription: inhibition of NF-kappa B, c-Fos, and c-Jun activities. 852 15

p202 is an interferon-inducible protein whose expression in transfected cells inhibits proliferation. p202 binds to the retinoblastoma tumor suppressor protein in vitro and in vivo and the transcription factors AP-1 c-Fos and c-Jun, NF-kappaB p50 and p65, and inhibits the transcriptional activity of these factors in vivo. Here we report that p202 nonspecifically binds to double-stranded DNA and to single-stranded DNA in vitro. Analysis with recombinant p202 revealed that DNA binding activity is intrinsic to p202. A C-terminal deletion mutant of p202 exhibited DNA-binding properties, indicating that the C-terminus is dispensable for DNA binding. We also found that underphosphorylated p202 efficiently binds to DNA. Our data suggest that DNA binding activity of p202 may contribute to its functions.
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PMID:The interferon-inducible growth-inhibitory p202 protein: DNA binding properties and identification of a DNA binding domain. 861 67

p202, an interferon-inducible murine protein, is a member of the "200 family" of proteins and is primarily nuclear. p202 is a modulator of transcription; it binds several transcription factors, including NF-kappaB p50 and p65, AP-1 c-Fos and c-Jun, and E2F1, and inhibits their transcriptional activity. p202 also binds pRb, the retinoblastoma protein, and if overexpressed it retards cell proliferation. Here we report that using the yeast two-hybrid assay we found that p202 bound the murine homolog of the human p53-binding protein 1 (53BP1), a protein shown to interact with the DNA binding domain of the p53 tumor suppressor protein. p202 bound a 98amino acid segment from 53BP1. This binding was inhibited by the replacement in p202 of a histidine (from the M(F/L)HATVA(T/S) sequence that is conserved among all of the 200 family proteins) by phenylalanine. We also report that overexpression of p202 inhibited the p53-dependent expression of reporter genes containing p53-activable segments from the mdm2 and p21 genes, whereas a decrease in the p202 level (in consequence of the expression of 202 antisense RNA) resulted in an increase in the p53-dependent expression of these reporters. Expression of the 53BP1 segment binding to p202 overcame the inhibition by overexpressed p202 of the transcription of reporters mediated by the p53 or the AP-1 transcription factors and of the proliferation of yeast.
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PMID:p202, an interferon-inducible modulator of transcription, inhibits transcriptional activation by the p53 tumor suppressor protein, and a segment from the p53-binding protein 1 that binds to p202 overcomes this inhibition. 891 Mar 40

p202 is a primarily nuclear, interferon-inducible murine protein that is encoded by the Ifi 202 gene. Overexpression of p202 in transfected cells retards cell proliferation. p202 modulates the pattern of gene expression by inhibiting the activity of various transcription factors including NF-kappaB, c-Fos, c-Jun, E2F-1, and p53. Here we report that p202 was constitutively expressed in mouse skeletal muscle and that the levels of 202 RNA and p202 greatly increased during the differentiation of cultured C2C12 myoblasts to myotubes. When overexpressed in transfected myoblasts, p202 inhibited the expression of one muscle protein (MyoD) without affecting the expression of a second one (myogenin). Thus, the decrease in the level of MyoD (but not of myogenin) during muscle differentiation may be the consequence of the increase in p202 level. Overexpressed p202 also inhibited the transcriptional activity of both MyoD and myogenin. This inhibition was correlated with an interaction of p202 with both proteins, as well as the inhibition by p202 of the sequence-specific binding of both proteins to DNA. This inhibition of the expression of MyoD and of the transcriptional activity of MyoD and myogenin may account for the inhibition of the induction of myoblast differentiation by premature overexpression of p202.
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PMID:Increase in p202 expression during skeletal muscle differentiation: inhibition of MyoD protein expression and activity by p202. 944 5

p202 is an interferon (IFN)-inducible, primarily nuclear, phosphoprotein (52-kDa) whose overexpression in transfected cells inhibits colony formation. p202 binds to the retinoblastoma tumor suppressor protein and two other members of the pocket family proteins (p107 and p130). Moreover, overexpression of p202 in transfected cells inhibits the transcriptional activity of E2Fs (E2F-1/DP-1 and E2F-4/DP-1), p53, AP-1 c-Fos and c-Jun, NF-kappaB p50 and p65. Here we demonstrate that inhibition of endogenous p202 production in murine AKR-2B fibroblasts did not result in an increase in cell proliferation. Instead, these cells exhibited increased susceptibility to apoptosis in response to decrease in serum concentrations in the growth medium. These observations are consistent with the notion that normal levels of p202 may be needed for the regulation of cell proliferation.
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PMID:p202 prevents apoptosis in murine AKR-2B fibroblasts. 964 35

Murine p202 is an interferon-inducible primarily nuclear phosphoprotein (52 kDa) whose expression in transfected cells inhibits colony formation. p202-binding proteins include the pocket proteins (pRb, p107 and p130), a p53-binding protein (sm53BP1), and transcription factors (e.g. NF-kappaB (p50 and p65), AP-1 (c-Fos and c-Jun), E2F-1, E2F-4, MyoD, and myogenin). p202 modulates the transcriptional activity of these factors in transfected cells. Here we demonstrate that p202 self-associates directly and a sequence in p202, which is conserved among the members of the 200-family proteins, was sufficient for self-association in vitro. Our observations reported herein raise the possibility that self-association of p202 may provide a mechanism for the regulation of its activity.
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PMID:p202 self-associates through a sequence conserved among the members of the 200-family proteins. 982 52

The Ifi202 gene is part of the interferon-activatable murine gene 200 cluster on chromosome 1. Ifi202 encodes the p202 protein whose overexpression is growth inhibitory and which can bind and inhibit the activity of numerous transcription factors including c-Jun, c-Fos, NF-kappaB, E2F-1, E2F-4, MyoD, and myogenin. We report here the exon-intron structure of Ifi202 and the discovery of Ifi202b and Ifi202c, close homologs of Ifi202 (whose designation we now change to Ifi202a). Ifi202a, b, and c were colocalized to chromosome 1 bands H4-H5 by fluorescence in situ hybridization. Ifi202b encodes p202b, which is interferon-inducible and differs from p202a in only 7 of 445 amino acids. 202b mRNA is constitutively expressed in tissues in which 202a mRNA is expressed. Ifi202c is apparently an unexpressed pseudogene. In murine embryonic fibroblasts (MEFs) from 129 mice, the level of 202b mRNA is approximately half that of 202a mRNA. We knocked out the Ifi202a gene from 129 mice. The expression of 202b mRNA, but not 202a mRNA, persisted in the knockout mice and their MEFs at the same level as in wildtype mice. However, in MEFs from the knockout mice, the constitutive and interferon-induced levels of p202b were approximately as high as the constitutive and the interferon-induced levels of p202a plus p202b, respectively, in MEFs from wildtype mice. These findings suggest dosage compensation at the posttranscriptional level. This might account for the apparent lack of phenotype of the knockout mice.
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PMID:Characteristics of three homologous 202 genes (Ifi202a, Ifi202b, and Ifi202c) from the murine interferon-activatable gene 200 cluster. 1049 28

Previous studies have revealed that p202 (52 kDa), an interferon (IFN) and differentiation-inducible protein, negatively regulates cell proliferation and modulates cell survival. However, the role of p202 in transformed cells remains to be investigated. Here we report that constitutive expression of oncogenic H-Ras (Q61L) in NIH 3T3 cells, which resulted in cell transformation, was associated with increases in the steady-state levels of 202 RNA and protein. Interestingly, the increase in p202 levels in transformed cells correlated with increases in the activity of the transcription factor c-Jun/AP-1, which bound to the two potential AP-1 DNA binding sites (the AP-1CS1 and AP-1CS2) in the 5'-regulatory region of the 202 gene in gel mobility shift assays. Furthermore, the site-directed mutagenesis, coupled with promoter-reporter analyses, revealed that these two AP-1 DNA binding sites contribute to the regulation of the 202 gene in Ras transformed cells. Because treatment of transformed cells with a specific inhibitor of MEK (PD 98059) resulted in significant decreases in the levels of p202, these observations raise the possibility that in transformed cells Ras/Raf/MEK pathway regulates the transcriptional activation of the 202 gene. Significantly, decreases in the levels of p202 in Ras transformed NIH 3T3 cells under reduced serum conditions increased the susceptibility to apoptosis. Collectively, our observations support the idea that the transcriptional increases in the levels of p202 by oncogenic H-Ras in NIH 3T3 cells are needed for cell survival.
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PMID:Induction of p202, a modulator of apoptosis, during oncogenic transformation of NIH 3T3 cells by activated H-Ras (Q61L) contributes to cell survival. 1246 88

Studies have revealed that increased expression of interferon (IFN)-inducible Ifi202 gene (encoding p202 protein) in splenic B and T cells from B6.Nba2 congenic (congenic for Nb2 locus derived from NZB mice) female mice is associated with lupus susceptibility. However, signaling pathways that regulate Ifi202 expression in immune cells remain to be elucidated. Here we report that stimulation of T cells up-regulates the Ifi202 expression. We found that steady-state levels of Ifi202 mRNA and protein were detectable in splenic T cells from NZB mice and stimulation of T cells with anti-CD3 and anti-CD28 up-regulated expression of the Ifi202 gene. Similarly, stimulation of cells of a mouse T cell hybridoma cell line (2B4.11) also activated transcription of the Ifi202 gene. Significantly, up-regulation of Ifi202 expression in stimulated T cells was inhibited by treatment of cells with SP600125, a specific inhibitor of c-Jun N-terminal kinase (JNK). Conversely, treatment of cells with anisomycin, a potent activator of the JNK and c-Jun, up-regulated Ifi202 expression. Consistent with the activation of JNK/c-Jun pathway by T cell stimulation, forced expression of c-Jun in 2B4 T cells and in mouse embryonic fibroblasts (MEFs) also up-regulated the Ifi202 expression. Furthermore, we found that stimulation of T cells increased association of the activated c-Jun to the 5'-regulatory region of the Ifi202 gene in chromatin immunoprecipitation assays (ChIPs). Together, our observations demonstrate that stimulation of T cells up-regulates the Ifi202 expression in part through the JNK/c-Jun pathway.
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PMID:Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway. 1837 89