Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biological effects of the p53 tumor suppressor protein are elicited, at least in part, through sequence-specific transactivation of a battery of target genes. The differential display method was employed towards identifying additional p53 target genes, with emphasis on genes whose induction may contribute to p53-mediated apoptosis. We report here the cloning of a novel p53-inducible gene, designated PAG608. PAG608 transcripts are induced by DNA damage in a p53-dependent manner. PAG608 encodes a nuclear zinc finger protein, which appears to localize preferentially to nucleoli when expressed at moderate levels in transfected cells. Transient overexpression of PAG608 in human tumor-derived cells leads to distinctive changes in nuclear morphology, and can promote apoptosis. Together with additional p53 target genes, PAG608 may therefore play a role in mediating the biological activities of p53.
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PMID:A novel p53-inducible gene, PAG608, encodes a nuclear zinc finger protein whose overexpression promotes apoptosis. 925 Jun 82

Wild type p53 expressed from a temperature-sensitive (ts p53) construct induces both G1 cell cycle arrest and apoptosis in the p53-negative J3D mouse T lymphoma line (Wang et al., 1995). Using differential display analysis, we have identified one new p53-induced gene, wig-1 (for wild type p53-induced gene 1), whose 7.6 kb and 2.2 kb transcripts are upregulated in ts p53-transfected J3D cells following induction of wild type p53 expression by temperature shift to 32 degrees C. The wig-1 transcripts were also induced in irradiated NIH3T3 and p21-/- fibroblasts but not in irradiated p53-/- fibroblasts. Whole body gamma irradiation caused induction of both wig-1 transcripts in mouse brain, testis, kidney, spleen and lung. A basal wig-1 expression was detected in brain, testis and kidney. The WIG-1 protein contains three zinc finger motifs and a putative nuclear localization signal.
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PMID:Wig-1, a new p53-induced gene encoding a zinc finger protein. 940 Sep 96

A brief, 3 min period of global forebrain ischemia in the rat, induced by bilateral common carotid occlusion combined with hypotension, confers resistance to hippocampal pyramidal neurons against a subsequent 10 min ischemia, which is normally lethal to these cells. The molecular mechanisms underlying this ischemic preconditioning, or tolerance, are poorly understood. The tumor suppressor p53 is a transcription factor implicated in neuronal death following various insults, including cerebral ischemia. p53 is activated in response to cellular stress, e.g. hypoxia and DNA damage. Using in situ hybridization, we investigated the hippocampal mRNA expression of p53, and two of its target genes, p21(WAF1/Cip1) and the recently cloned PAG608/Wig-1, in a two-vessel occlusion model of ischemic preconditioning. We also evaluated changes in the protein levels of p53 and PAG608/Wig-1 using immunohistochemistry. The mRNA levels of all three genes increased in the ischemia sensitive CA1 region both following 3 min (non-lethal) preconditioning and 10 min of (lethal) nonconditioned ischemia. In contrast, after 10 min of ischemia preconditioned by a 3 min ischemic insult 48 h earlier, no upregulation of these genes was detected in the CA1. Following 10 min of nonconditioned ischemia, increased neuronal immunostaining of p53 and PAG608/Wig-1 was observed in the hippocampus, which was less pronounced following 3 min of preconditioning ischemia and 10 min of preconditioned ischemia. Our results demonstrate that activation of p53 and its response genes p21(WAF1/Cip1) and PAG608/Wig-1 occurs in the brain following lethal as well as non-lethal ischemic insults, and that ischemic preconditioning markedly diminishes this activation.
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PMID:Activation of p53 and its target genes p21(WAF1/Cip1) and PAG608/Wig-1 in ischemic preconditioning. 1040 80

In this report, we describe the cloning of the coding region of human WIG-1 cDNA. The human 8 and 6 kb WIG-1 transcripts are both upregulated following ionizing irradiation of the human colon cancer cell lines HCT116 and LoVo which have wild type TP53 but not in DLD1 cells that lack wild type TP53. Basal levels of both WIG-1 transcripts were detected in human adult brain, kidney, and testis, but not in fetal brain, heart, pancreas, adrenal gland, fetal liver, and small intestine. FISH analysis mapped the human WIG-1 gene to 3q26.3. Investigation of squamous cell carcinomas of the lung by Southern blot and semiquantitative RT-PCR analysis showed amplification in combination with increased expression of WIG-1 in 1/7 tumors and increased expression in a further two cases.
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PMID:Cloning and chromosomal localization of human WIG-1/PAG608 and demonstration of amplification with increased expression in primary squamous cell carcinoma of the lung. 1168 94

The p53-activated gene PAG608, which encodes a nuclear zinc finger protein, is a p53-inducible gene that contributes to p53-mediated apoptosis. However, the mechanisms by which PAG608 is involved in the apoptosis of neuronal cells are still obscure. In this study, we demonstrated that expression of p53 was induced by 100 microm 6-hydroxydopamine (6-OHDA), accompanied by increased PAG608 expression in PC12 cells. On the other hand, transient or permanent transfection of antisense PAG608 cDNA into PC12 cells significantly prevented apoptotic cell death induced by 100 microm 6-OHDA or 200 microm hydrogen peroxide but not by 250 microm 1-methyl-4-phenylpyridinium ion. The 6-OHDA-induced activation of caspase-3, DNA fragmentation, loss of mitochondrial membrane potential, and induction of p53 and Bax were also prevented in PC12 cells that stably expressed antisense PAG608 cDNA. These results suggest that PAG608 is associated with the apoptotic pathway induced by these oxidative stress-generating reagents, upstream of the collapse in the mitochondrial membrane potential in PC12 cells. Interestingly, transient transfection with PAG608 cDNA increased p53 expression in both PC12 cells and B65 cells, indicating that PAG608 induced by p53 is able to induce p53 expression in these cells inversely. Furthermore, transient transfection of a truncated mutant PAG608 cDNA, lacking the first zinc finger domain, inhibited 6-OHDA-induced cell death and altered the nuclear and nucleolar localization of wild-type PAG608 in PC12 cells. These results suggest that PAG608 may induce or regulate p53 expression and translocate to the nucleus and nucleolus using its first zinc finger domain during oxidative stress-induced apoptosis of catecholamine-containing cells.
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PMID:The p53-activated gene, PAG608, requires a zinc finger domain for nuclear localization and oxidative stress-induced apoptosis. 1219 12

We have efficiently generated the first monoclonal antibody (MAb) against the human WIG-1 (wild-type p53-induced gene 1) protein, an apoptosis-related protein consisting of three zinc finger domains. Protein A affinity chromatography was performed to purify MAb from mice production ascites. Hybridomas were screened by indirect enzyme-linked immunosorbent assay (ELISA). One MAb designated GW-3E4 (IgG1), effective in detecting the nuclear protein in human esophageal squamous cell carcinoma (ESCC) tissues and EC109 cell line, was characterized by ELISA and Western immunoblotting. Thus, it binds to native WIG-1 protein and should be useful in studies of WIG-1 protein function and expression. By Western immunoblotting analysis of 20 patients with ESCC using the MAb, we found that the expression of WIG-1 protein in tumor tissue was significantly higher than in incision margin. The results showed that WIG-1 might be a novel modifier in esophageal carcinogenesis, and the WIG-1 MAb should be useful in further study of the mechanism in WIG-1-related physiological reactions.
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PMID:Preparation of a novel monoclonal antibody specific for WIG-1 and detection of its expression pattern in human esophageal carcinoma. 2105 45

TP53 is a critical tumor suppressor that is mutated in approximately 50% of human cancers. Unveiling the downstream target genes of TP53 that fulfill its tumor suppressor function is an area of intense investigation. Zmat3 (also known as Wig-1 or PAG608) is one such downstream target of p53, whose loss in hemopoietic stem cells lacking the apoptosis and cell cycle regulators, Puma and p21, respectively, promotes the development of leukemia. The function of Zmat3 in tumorigenesis however remains unclear. Here, to investigate which oncogenic drivers co-operate with Zmat3 loss to promote neoplastic transformation, we utilized Zmat3 knockout mice in models of c-MYC-driven lymphomagenesis and KrasG12D-driven lung adenocarcinoma development. Interestingly, unlike loss of p53, Zmat3 germline loss had little impact on the rate of tumor development or severity of malignant disease upon either the c-MYC or KrasG12D oncogenic activation. Furthermore, loss of Zmat3 failed to rescue KrasG12D primary lung tumor cells from oncogene-induced senescence. Taken together, we conclude that in the context of c-MYC-driven lymphomagenesis or mutant KrasG12D-driven lung adenocarcinoma development, additional co-occurring mutations are required to resolve Zmat3 tumor suppressive activity.
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PMID:Consequences of Zmat3 loss in c-MYC- and mutant KRAS-driven tumorigenesis. 3308 33