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)

Activation of the p53 tumor suppressor protein can lead to either cell cycle arrest or apoptosis. Several functional domains necessary for mediating cell cycle arrest and apoptosis in p53 have been mapped, e.g., the proline-rich domain. The proline-rich domain is located within residues 60-90, which comprise five PXXP motifs (where P represents proline and X any amino acid). To further delineate the function of the proline-rich domain and its potential role in transactivation, we generated several groups of cell lines that inducibly express various p53 mutants using a tetracycline-regulated expression system. We found that p53(delta62-91), which lacks all five PXXP motifs in human p53, is capable of inducing cell cycle arrest but not apoptosis, while p53(gln22-ser23/delta62-91), which contains a double point mutation in the activation domain as well as deletion of the proline-rich domain, completely loses its activity. However, p53(delta74-91), which contains only one PXXP motif at its N-terminus, is not only capable of inducing cell cycle arrest but also retains a partial apoptotic activity. Furthermore, we found that deletion of the proline-rich region has no or very mild effects on activation of several transiently transfected p53 target gene promoters, i.e., the p21, MDM2, BAX, and GADD45 promoters. However, such deletion differentially affects p53 induction of endogenous target genes, i.e., induction of p21, MDM2, BTG2, p85, PIG3, PIG6 and PIG11 was reduced or abrogated but induction of BAX, KILLER/DR5, PIG2, PIG7 and PIG8 was not substantially affected. Interestingly, induction of GADD45 was enhanced. These results suggest that the proline-rich region may play a role in chromatin remodeling, which counteracts chromatin-mediated repression for some of the endogenous p53 target genes.
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PMID:Differential regulation of cellular target genes by p53 devoid of the PXXP motifs with impaired apoptotic activity. 1032 40

Using a cDNA microarray consisting of 23,040 genes, we analyzed gene-expression profiles of ovarian endometrial cysts from 23 patients in order to identify genes involved in endometriosis. By comparing expression patterns between endometriotic tissues and corresponding eutopic endometria, we identified 15 genes that were commonly up-regulated in the endometrial cysts during both proliferative and secretory phases of the menstrual cycle, 42 that were up-regulated only in the proliferative phase, and 40 that were up-regulated only in the secretory phase. The up-regulated elements included genes encoding some HLA antigens, complement factors, ribosomal proteins, and TGFBI. On the other hand, 337 genes were commonly down-regulated throughout the menstrual cycle, 144 only in the proliferative phase, and 835 only in the secretory phase. The down-regulated elements included the tumor suppressor TP53, genes related to apoptosis such as GADD34, GADD45A, GADD45B and PIG11, and the gene encoding OVGP1, a protein involved in maintenance of early pregnancy. Semi-quantitative RT-PCR experiments supported the results of our microarray analysis. These data should provide useful information for finding candidate genes whose products might serve as molecular targets for diagnosis or treatment of endometriosis.
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PMID:Genome-wide cDNA microarray analysis of gene-expression profiles involved in ovarian endometriosis. 1257 8

Arsenic trioxide (As2O3) has been used as an effective chemotherapy agent for some human cancer, such as acute promyelocytic leukemia. We have demonstrated that low level of As2O3 relatively selectively inhibited growth of the solid tumor MGC-803 cells by triggering apoptosis. In this study, we found PIG11, a p53-induced gene, was upregulated markedly by As2O3 using the technique of differential display reverse transcriptase PCR (DDRT-PCR). Addition of anti-PIG11 phosphorothioated oligonucleotide (5'-GGC CGC CAT CTT CTC CTC-3') before As2O3 treatment, abolished the transient increase in PIG11 gene expression. Furthermore, it significantly inhibited the As2O3-induced apoptosis of MGC-803 cells, but had no effect in addition of missense (5'-GAG GAG AAG ATG GCG GCC-3') phosphorothioated oligonucleotides. These results suggest that PIG11, as a downstream target of p53, is involved in apoptosis of MGC-803 cells.
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PMID:P53-induced gene 11 (PIG11) involved in arsenic trioxide-induced apoptosis in human gastric cancer MGC-803 cells. 1288 91

The tumor suppressor p53 regulates the expression of various genes that promote apoptosis. PIG11 (P53-induced gene 11), also referred to as TP53I11 (tumor protein p53 inducible protein 11), is a direct p53 target gene. Recent data demonstrated that PIG11 was up-regulated markedly in arsenic trioxide induced apoptosis by DDRT-PCR, suggesting a new class of p53 target genes that sensitize cells to the effects of chemotherapeutic agents. In this study, through the construction of a recombinant GFP-PIG11 expression vector and transfection of HEK293 cells with GFP or GFP-PIG11, the role of PIG11 in apoptosis was analyzed. Results demonstrated that the percentage (11.38%) of apoptotic cells with GFP-PIG11 transfection was higher than that (7.28%) of with only GFP transfection (P<0.05). At 24 h after 1 microM of arsenic trioxide treatment, apoptotic cells exhibited a significant increase in the expression of GFP-PIG11 (36.67%+/-2.78), in contrast, 10.50%+/-2.03 only GFP and 5.25%+/-0.96 vehicle control (P<0.01). In addition, we showed that intracellular content of reactive oxygen species (ROS) was 9.66+/-0.52 in GFP-PIG11 transfection, higher than 5.21+/-0.08 in GFP only and 5.99+/-0.45 in vehicle control (P<0.01). The above results suggest that overexpression of PIG11 could induce cell apoptosis in the low levels and enhanced the apoptotic effects of arsenic trioxide. The process could be involved in intracellular generation of ROS.
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PMID:A P53 target gene, PIG11, contributes to chemosensitivity of cells to arsenic trioxide. 1522 15

PIG11 (p53-induced protein 11), one of early transcriptional targets of tumor suppressor p53, was up-regulated in the induction of apoptosis or cell growth inhibition by multiple chemopreventive agents. However, its biological role remains unclear. Here, we expressed His(6)-tagged PIG11 protein in Escherichia coli and demonstrated the recombinant His(6)-tagged PIG11 protein could bind to supercoiled and relaxed closed circular plasmid DNA or linear DNA with different length using gel retardation assays in vitro. The interaction between DNA and PIG11 protein was sequence-independent and related to charge effect. The reducing thiol group in PIG11 protein was involved in the binding activity of PIG11 to DNA. Furthermore, the images of atomic force microscopy directly confirmed the binding of DNA and PIG11 protein and showed the PIG11-DNA complex formed a beads-on-a-string appearance in which PIG11 protein associated with DNA as polymer. These findings suggest that PIG11 protein may play an important role by interaction with other biological molecules in the regulation of apoptosis and provided us a novel angel of view to explore the possible function of PIG11 in vivo.
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PMID:PIG11 protein binds to DNA in sequence-independent manner in vitro. 1748 69

PIG11 (p53-induced gene 11) is a p53 target gene and candidate tumour suppressor gene. In this study, the expression of PIG11 protein was detected in human hepatocellular carcinoma (HCC) and normal liver tissues with an immunohistochemical method. Compared with expression in human normal liver tissues, the expression of PIG11 protein was significantly down-regulated in human HCC tissues. In addition, a recombinant pLXSN-PIG11 retroviral vector was constructed and transfected into HepG2 cells (human hepatocellular carcinoma cell line) and the role of PIG11 in apoptosis was analyzed. The percentage (18.60%) of apoptotic cells transfected with pLXSN-PIG11 was higher than that in cells transfected with pLXSN only (6.03%) or the vehicle control (3.81%) (P < 0.01). DNA gel electrophoresis showed a clear DNA ladder in pLXSN-PIG11-infected HepG2 cells. Our results suggested that the PIG11 gene is involved in carcinogenesis and development of hepatocarcinoma. Therefore, PIG11 is considered to be a new candidate liver tumour suppressor gene, and may play an important role in tumour suppression through promotion of cell apoptosis.
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PMID:PIG11 is involved in hepatocellular carcinogenesis and its over-expression promotes Hepg2 cell apoptosis. 1909 15

P53-induced protein 11 (PIG11), one of the primeval transcriptional targets of p53, is up-regulated in apoptosis induced by multiple chemopreventive agents and is involved in tumorigenesis or tumor development. Nevertheless, the clinical value and biological role of PIG11 in hepatocellular carcinoma (HCC) are still unknown. In the present article, we explored the expression pattern of PIG11 in HCC tumor tissues, the prognostic value of PIG11 for HCC patients, and the biological functions on the apoptosis of HepG2 cells. We discovered that high PIG11 expression was negatively associated with certain clinical characteristics, and higher expression of PIG11 resulted in better prognosis of patients with HCC. PIG11 over-expression induced HepG2 cell apoptosis through the mitochondrial pathway, and reactive oxygen species played a regulatory role in this process. Hence, PIG11 may act as a candidate liver tumor suppressor and exhibit potential as a novel prognostic biomarker for HCC.
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PMID:PIG11 over-expression predicts good prognosis and induces HepG2 cell apoptosis via reactive oxygen species-dependent mitochondrial pathway. 3024 Oct 46