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 TP53 tumor suppressor gene regulates a number of genes that are involved in cell-cycle inhibition, apoptosis, and maintaining genetic stability. Recently, two genes that have a role in immunosurveillance were identified as downstream targets of TP53. These genes, TAP1 and fractalkine, may contribute to suppress tumor growth through host immunosurveillance. It has been reported that the mouse secreted phosphoprotein osteopontin (Opn) is one of the key cytokines for type 1 immune responses mediated by macrophages. It also was reported that Opn may play a role in suppressing tumor growth in vivo. Here we identified Opn as a Tp53-target gene using mRNA differential display analysis of embryonic fibroblasts from Tp53-deficient mice. Furthermore, we found that Opn expression was upregulated by DNA damage-induced Tp53 activity and by adenovirus-mediated transfer of the human TP53 gene. In addition, a luciferase assay showed that the Opn gene has a functional Tp53-responsive element in its promoter region, and a chromatin immunoprecipitation assay confirmed interaction between the Opn promoter and Tp53 protein in vivo. These results suggest that OPN is a direct transcriptional target of TP53. The TP53-directed regulation of OPN expression suggests a novel model of TP53 participation in immunosurveillance, involving interaction with the host immune system to prevent damaged cells from undergoing malignant transformation.
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PMID:Identification of the osteopontin gene as a direct target of TP53. 1180 84

The p53 tumor-suppressor gene, encoding a phosphoprotein, is a key element in maintaining genomic stability and cell apoptosis. It is also implicated in nervous-system development. In order to examine the role of the p53 gene for the pathogenesis of schizophrenic disorders, patients (n=155) and control subjects (n=168) were genotyped for the p53-Pro72Arg polymorphism. The results demonstrated no association with schizophrenia and/or age of onset for this polymorphism.
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PMID:Association study of the p53-gene Pro72Arg polymorphism in schizophrenia. 1181 47

Sixty-two follicular adenomas of the thyroid were investigated by immunohistochemistry for the expression of p53, MDM2 and bcl-2 proteins. The wild type of 393 aminoacid nuclear p53 phosphoprotein is the product of a gene located on the short arm of chromosome 17. The p53 protein controls the growth of transformed cells in a culture and thus termed a suppressor gene product. Mouse double minute 2 (MDM2) gene product has been described to occur in malignant epithelial tissue, the protein product of this gene binds to and presumably inactivates the growth suppressive effect of wild type p53 protein. Bcl-2 is an oncogene whose product inhibits apoptosis in many cells types. Some scattered nuclei in two adenomas (3.2%) stained positively for p53. The adenomas with positive staining for p53 were subserially sectioned, but no signs of invasion were found, both patients are alive and well. In 12 adenomas (19%) there was positive reaction for MDM2 protein, whereas none of them where p53 positive. All cases were strongly positive for bcl-2 staining. We conclude that p53 protein expression is not confined to follicular adenomas, while MDM2 and bcl-2 genes products are.
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PMID:p53, MDM2, bcl-2 staining in follicular neoplasms of the thyroid gland. 1182 May 89

Mdm2 is a p53-inducible phosphoprotein that negatively regulates p53 by binding to it and promoting its ubiquitin-mediated degradation. Alternatively spliced variants of Mdm2 have been isolated from human and mouse tumors, but their roles in tumorigenesis, if any, remain elusive. We cloned six alternatively spliced variants of Mdm2 from E(mu)-Myc-induced mouse lymphomas, all of which lacked the NH(2)-terminal p53-binding domain but conserved the remainder of the Mdm2 protein. Enforced expression of full-length Mdm2 in primary mouse embryo fibroblasts or bone marrow-derived, interleukin 7-dependent pre-B cells accelerated their proliferation, whereas unexpectedly, overexpression of truncated Mdm2 isoforms inhibited their growth. Truncated variants were active as inhibitors whether they localized predominantly to the nucleus or cytoplasm. Despite the absence of the p53-binding domain, growth inhibition remained strictly p53 dependent (but not p19(Arf) dependent) and could be overcome by full-length Mdm2. The intact RING finger domain at the Mdm2 COOH terminus (amino acids 399-489) was necessary and sufficient for growth inhibition by truncated Mdm2 proteins and could physically interact with either the RING finger domain or central acidic region of full-length Mdm2. However, such interactions do not inhibit Mdm2 E3 ubiquitin ligase activity in vitro using p53 as a substrate. Expression of growth-inhibitory Mdm2 isoforms in tumors remains an enigma.
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PMID:The RING domain of Mdm2 can inhibit cell proliferation. 1186 7

SV40 large T antigen associates with a cellular phosphoprotein, p53, in virus-transformed cells. We have raised three new monoclonal antibodies, PAb1101, PAb1102 and PAb1103, to this cellular protein, derived from SV40-transformed human fibroblasts. These define at least two non-overlapping determinants on human p53 that are in different areas of the molecule from those recognised by previously available antibodies. Unlike those antibodies, PAb1102 and PAb1103 do not react with rodent p53. PAb1101 reacts far more weakly with rodent p53 than with primate p53. All three antibodies show a preference for binding to the large T-associated form of p53, an effect that is particularly marked with PAb1102. The novel specificity of these antibodies allows further probing of the nature and function of the large T/p53 complex in human cells.
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PMID:Monoclonal antibodies displaying a novel species specificity for the primate transformation-related protein, p53. 1189 96

Among the hepatotropic viruses, hepatitis C virus (HCV) is considered to be the leading cause of liver disease in humans, affecting approximately 2% of the world population. HCV-encoded nonstructural protein 5A (NS5A) is a 56-58-kDa phosphoprotein, which is produced from the processing of viral polyprotein. The potential mechanism(s) by which NS5A is able to influence key cellular processes are largely unknown. In this study, we investigated the functional properties of NS5A. In vivo co-immunoprecipitation and pull-down assays demonstrated that NS5A forms a heteromeric complex with TATA box binding protein (TBP) and tumor suppressor protein p53. Mutants of TBP and p53 showed reduced binding to NS5A. To determine the functional relevance of these associations, we found that NS5A inhibits the binding of both p53 and TBP to their DNA consensus binding sequences in vitro. NS5A also inhibited the p53-TBP and p53-excision repair cross complementing factor 3 (ERCC3) protein-protein complex formation. Furthermore, NS5A repressed the p53 regulated p21 (WAF1) promoter and a synthetic promoter containing multiple p53 responsive DNA elements binding sites in HCT116 p53(+/+) cell line. p53-mediated transcriptional activation from both promoters was reduced approximately 3-5-fold following expression of NS5A. Taken together, these results suggest that NS5A may exert its influence on key cellular processes by functional associations with p53 and TBP. This could explain one of the possible mechanism(s) by which NS5A is able to exert its effect on cellular gene expression and cell growth regulation.
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PMID:Hepatitis C virus NS5A protein binds TBP and p53, inhibiting their DNA binding and p53 interactions with TBP and ERCC3. 1237 83

The purpose of this study was to evaluate the extent to which the expression of p53, c-myc, bcl-2, ras genes and chromosomes, along with activity of hTERT, impacts on the malignant transformation of immortalized esophageal epithelial cells. The SHEE cell line was established from an embryonic esophageal epithelial cell induced by transduction of E6E7 genes of human papillomavirus type 18 (HPV18E6E7). In cells of the 85th passage (SHEE85), the malignant transformation of SHEE was confirmed by morphology, cell proliferative index and tumor formation in SCID mice. C-myc, p53, bcl-2 and ras genes were assayed by the multi-PCR method with house-keeping gene GAPDH as control. The modal number of chromosomes was analyzed and its expression of subunit of telomerase, hTERT, was assessed by RT-PCR. Expression of HPV18E6E7 was assayed by Western blotting. The results showed that cells of SHEE85 were atypical and exhibited proliferative status with a proliferation index of 45.70%. Tumors formed in SCID mice with invasion of adjacent tissue. The karyotype belonged to hypotriploid and displayed expression of hTERT. C-myc, k-ras, bcl-2 and p53 (expression of phosphoprotein) were positive in SHEE85. Expression of HPV18E6E7 was positive. Taken together, SHEE85 cells were in fully malignant transformation and their molecular mechanism involved the expression of cellular genes, such as p53, bcl-2, c-myc and ras, and aberrance of chromosomes. It is probable that all of these changes were related with HPV18E6E7.
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PMID:Cytogenetic and molecular genetic changes in malignant transformation of immortalized esophageal epithelial cells. 1285 21

Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that has a broad host range in warm-blooded animals, probably including humans. Recently, it was demonstrated that a 24-kDa phosphoprotein (P) of BDV directly binds to a multifunctional protein, amphoterin-HMGB1, and inhibits its function in cultured neural cells (W. Kamitani, Y. Shoya, T. Kobayashi, M. Watanabe, B. J. Lee, G. Zhang, K. Tomonaga, and K. Ikuta, J. Virol. 75:8742-8751, 2001). This observation suggested that expression of BDV P may cause deleterious effects in cellular functions by interference with HMGB1. In this study, we further investigated the significance of the binding between P and HMGB1. We demonstrated that P directly binds to the A-box domain on HMGB1, which is also responsible for interaction with a tumor suppression factor, p53. Recent works have demonstrated that binding between HMGB1 and p53 enhances p53-mediated transcriptional activity. Thus, we examined whether BDV P affects the transcriptional activity of p53 by interference with HMGB1. Mammalian two-hybrid analysis revealed that p53 and P competitively interfere with the binding of each protein to HMGB1 in a p53-deficient cell line, NCI-H1299. In addition, P was able to significantly decrease p53-mediated transcriptional activation of the cyclin G promoter. Furthermore, we showed that activation of p21(waf1) expression was repressed in cyclosporine-treated BDV-infected cells, as well as p53-transduced NCI-H1299 cells. These results suggested that BDV P may be a unique inhibitor of p53 activity via binding to HMGB1.
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PMID:Borna disease virus phosphoprotein represses p53-mediated transcriptional activity by interference with HMGB1. 1458 61

The tumour suppressor protein p53 is a phosphoprotein that is activated by DNA damage. It is involved in the decision whether the cells should stop replication and proceed to repair their DNA, or to die by apoptosis. In the present study, we evaluate the effect of some treatment modalities on the expression of p53 in facial skin. Biopsy specimens were obtained from the facial skin of 20 patients before and after treatment using topical tretinoin (11 cases), TCA chemical peeling (5 cases) and dermabrasion (4 cases). Biopsy specimens were also obtained from 12 control subjects representing the same age groups of the patients. Topical tretinoin therapy was found to induce a significant decrease in the expression of p53 up to 6 months of therapy followed by a significant increase after 10 months of therapy. On the contrary, superficial TCA peeling did not induce any statistically significant change in the expression of p53. On the other hand dermabrasion was found to induce a significant decrease in the level of expression of p53 in biopsies obtained after complete re-epithelialization followed by a significant increase. These changes in the expression of p53 may play a role in mediating the effects of such treatment modalities on the epidermis, as well as prevention of actinic neoplasia by adjusting any disturbance in the proliferation/apoptosis balance observed in photoaged facial skin.
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PMID:Effect of topical tretinoin, chemical peeling and dermabrasion on p53 expression in facial skin. 1469 85

Results presented in this study demonstrate that treatment of MCF-7 cells with taxol resulted in induction of estrogen receptor-alpha (ER alpha) gene transcription with a subsequent increase in ER alpha mRNA; this effect was promoter specific since taxol did not affect total transcription in MCF-7 cells and lacked an effect on transcription of the human acidic ribosomal phosphoprotein protein PO, progesterone receptor, and pS2 genes. In contrast to the increase in transcription of the ER alpha gene, taxol inhibited translation of the ER alpha mRNA. This effect is also transcript specific since taxol did not alter total protein synthesis and did not affect the concentration of progesterone receptor protein in the cell. The overall result of taxol treatment was to decrease the concentration of ER alpha protein in the MCF-7 cells. Evidence is presented that the effects of taxol on ER alpha gene transcription may be mediated through the induction of p53.
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PMID:Regulation of estrogen receptor-alpha expression in MCF-7 cells by taxol. 1501 3


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