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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection of normal human diploid fibroblasts (HF) with the DNA tumor virus simian virus 40 (SV) leads to an extension of lifespan and concomitant increase in the levels of the viral large tumor antigen (T antigen) and the cellular protein p53. The intracellular localization of T antigen and p53 was mostly nuclear in both SVpre-crisis and SVpost-crisis cells, however certain population doubling (PD) of the SVpre-crisis cells exhibited some cytoplasmic staining. The DNA content of SVpre-crisis cells shifted to tetraploidy and the SVpost-crisis cells were near-tetraploid. Quantitation of T antigen and p53 in single cells by flow cytometry demonstrated that for all antibodies tested the levels of T antigen were higher in the SVpre-crisis HF than in the SVpost-crisis. The quantity of p53 increased with increasing age of SVpre-crisis HF, and the levels of p53 were higher in the SVpost-crisis HF populations. Immunoprecipitation of p53, T antigen and complexes demonstrated that all p53 was bound to T antigen in SVpre-crisis HF and SVpost-crisis HF. The SVpre-crisis HF cells showed that 33% of all T antigen was bound to p53, while 67% was free, and the SVpost-crisis HF exhibited 50% free T antigen and 50% bound to p53. The half-life of p53 was similar in all SVpre-crisis HF; however, the half-life was 2-3 times greater in SVpost-crisis HF than in SVpre-crisis HF. These results suggest that the interaction of DNA (ploidy), T antigen, p53 and complexes may be involved in formation of a stable SV40-transformed human cell line.
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PMID:T antigen and p53 in pre- and post-crisis simian virus 40-transformed human cell lines. 165 67

Infection of quiescent rat kidney cells with human adenovirus is shown to transcriptionally stimulate (transactivate) the p53 oncogene. The increased transcription results in an accumulation of p53-specific mRNA in parallel with an increase in p53 protein levels, although there is a considerable delay between transcriptional activation and the detection of stable p53 mRNA and protein. The induction of p53 is detectable with two monoclonal antibodies recognizing different epitopes. The induction of p53 by adenovirus is delayed compared to induction by serum, and it occurs after the onset of adenovirus-induced cellular DNA replication. Thus, adenovirus-induced DNA replication bypasses a G0/G1 control point. Experiments with hydroxyurea show that p53 activation does not require continued cell cycling and thus is likely to be a direct consequence of viral gene expression. Finally, the induction of p53 is shown to be dependent on expression of the 289-residue product encoded by the viral E1a gene.
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PMID:Transactivation of the p53 oncogene by E1a gene products. 214 58

Skin fibroblasts (SFs) from patients with adenomatosis of the colon and rectum (ACR) were shown, in general, to express elevated amounts of the p53 antigen as determined by immunoprecipitation with the monoclonal antibody PAb421. Infection with simian virus 40 (SV40) induced expression of the p53 antigen in SFs from normal individuals and further amplified its expression in ACR cells. The half-lives of the p53 antigen in mock-infected ACR cells and in SV40-transformed normal or ACR cells were about 2 and 15 hours, respectively. No immediate differences were detected in the coding segment of the human p53 gene between normal and ACR cells by either Southern or Northern blot analysis. These results suggest that over-expression of the p53 antigen is due, in part, to the increased stability of the p53 antigen in ACR cells. Over-expression represents an early event that is possibly associated with initiation and promotion of inherited colon cancer.
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PMID:Elevated levels of p53 antigen in cultured skin fibroblasts from patients with hereditary adenocarcinoma of the colon and rectum and its relevance to oncogenic mechanisms. 346 15

Metabolic stabilization of the tumor suppressor p53 is a key event in cellular transformation by simian virus 40 (SV40). Expression of the SV40 large tumor antigen (large T) is necessary but not sufficient for this process, as metabolic stabilization of p53 complexed to large T in abortively SV40-infected cells strictly depends on the cellular systems analyzed (F. Tiemann and W. Deppert, J. Virol. 68:2869-2878, 1994). Comparative analyses of various cells differing in metabolic stabilization of p53 upon abortive infection with SV40 revealed that metabolic stabilization of p53 closely correlated with expression of the SV40 small t antigen (small t) in these cells: 3T3 cells do not express small t and do not stabilize p53 upon infection with wild-type SV40. However, ectopic expression of small t in 3T3 cells provided these cells with the capacity to stabilize p53 upon SV40 infection. Conversely, precrisis mouse embryo cells express small t and mediate metabolic stabilization of p53 upon infection with wild-type SV40. Infection of these cells with an SV40 small-t deletion mutant did not lead to metabolic stabilization of p53. Small-t expression and metabolic stabilization of p53 correlated with an enhanced transformation efficiency by SV40, supporting the conclusion that at least part of the documented helper effect of small t in SV40 transformation is its ability to promote metabolic stabilization of p53 complexed to large T.
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PMID:Cooperation of simian virus 40 large and small T antigens in metabolic stabilization of tumor suppressor p53 during cellular transformation. 766 15

The data on the etiological factors presented here may enable us to suggest a synergism between the various factors associated with the pathogenesis of cervical cancer. Infection of the cervix by HPV 16/18 may result in persistence of viral DNA. The persistent HPV-DNA undergoes disruption at the E2 region, when integrated into the host genome. The transcriptional products E6 and E7 oncoproteins bind to and cause the degradation of p53 and Rb tumor-suppressor gene products. It is possible that, at that point, other cofactors may be involved in the progression toward a precancerous or cancerous condition. Those cofactors may include cigarette smoking, by introducing co-carcinogens to the tissue or by suppressing the local or systemic immune resistance similar to the effect of depressed immune resistance seen in AIDS or immunosuppression of transplant patients; hormones, by enhancing growth of HPV and transformation of HPV infected cells; low serum vitamin levels leading to decreased tissue resistance; or other infections causing local inflammation and the production of free radicals. CIN develops, leading eventually to cervical cancer.
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PMID:Etiology of cervical cancer: current concepts. 773 27

Adenovirus E1B 19K protein prevents premature death of adenovirus-infected cells. Viral mutants (19K mutants) defective in the 19K protein induce enhanced cell death, resulting in fragmentation of viral and cellular DNA. The 19K protein can also suppress the effects of certain external cell death-inducing stimuli, such as tumor necrosis factor alpha and various DNA-damaging agents that induce apoptosis. We have examined viral infection of permissive human cells and nonpermissive rat cells to determine if the 19K mutant induces apoptotic or necrotic type of cell death. Infection of normal rat kidney cells with an adenovirus type 2 19K deletion mutant induces internucleosomal DNA fragmentation and condensation of nuclear chromatin. Electron microscopic examination of these cells revealed the presence of condensed subnuclear bodies characteristic of apoptosis. In contrast, infection of human A549 cells induces random DNA fragmentation, and these cells do not exhibit characteristic condensation of the nuclear chromatin but contain enlarged nuclei loaded with virus particles. Therefore, it appears that adenovirus infection induces both apoptotic and necrotic types of cell death, depending on the cell type. Both types of cell death can be suppressed by E1B 19K protein. Similarly, a recombinant adenovirus expressing the human Bcl-2 protein but lacking the E1B proteins can efficiently suppress both apoptotic and necrotic cell death induced by adenovirus infection. The requirement of p53 tumor suppressor protein in adenovirus-induced cell death was investigated by infection of human Saos2 and mouse p53 nullizygous (p53-/-) cells lacking p53 tumor suppressor protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:p53-independent apoptotic and necrotic cell deaths induced by adenovirus infection: suppression by E1B 19K and Bcl-2 proteins. 775 71

Infection by human immunodeficiency virus type 1 (HIV-1) causes acquired immunodeficiency syndrome (AIDS) after a long clinical latency. This disease is associated with a spectrum of cancers. Here we report that wild-type p53 is a potent suppressor of Tat, a major transactivator of HIV-1. Reciprocally, Tat inhibits the transcription of p53. Downregulation of p53 by upregulated tat may be important for the establishment of productive viral infection in a cell and also may be involved in the development of AIDS-related malignancies.
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PMID:Reciprocal modulations between p53 and Tat of human immunodeficiency virus type 1. 777 31

Infections with high-risk strains of human papillomaviruses (HPVs) and with herpes simplex virus type 2 (HSV 2), as well as inactivation of the p53 tumor suppressor gene, are important cofactors in cervical carcinogenesis. We analyzed 41 paraffin-embedded cervical intraepithelial lesions, including 25 cases of low-grade cervical intraepithelia neoplasia (CIN), and 16 cases of high-grade CIN for the presence of HPV 16/18 and HSV 2 genomic sequences and for the nuclear accumulation of the p53 protein. HPV 16 DNA was detected in 24.% of low-grade CINs and in 43.7% of high-grade CINs. HPV 18 was found only in 8.% of low-grade CINs. None of the cases tested scored positive for HSV 2 DNA. Nuclear accumulation of p53 was found in 4% of low-grade CINs, and in 31.2% of high-grade CINs, including 57.1% of the lesions that were positive for HPV 16. These results indicate that HPV 16 infection was over sixfold more common than HPV 18 infection and that p53 overexpression was significantly associated with high-grade lesions.
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PMID:p53 expression and genetic evidence for viral infection in intraepithelial neoplasia of the uterine cervix. 783 72

Infection by Trichinella spiralis induces host muscle cells to become repositioned within the cell cycle and to lose differentiated skeletal muscle characteristics. Antibodies to a 43-kDa excretory-secretory (ES) protein (p43) also bind to infected host cell nuclei. Neither the identity of these nuclear antigens nor their role in inducing the infected cell phenotype is known. To address these issues, infected cell nuclei were isolated and nuclear antigens analyzed with several antibody preparations to p43. Four antibody preparations to p43 recognized 43-, 45-, 50-, 67- and 71-kDa proteins in ES extracts. The prominent proteins recognized by these antibodies in host nuclear antigen extracts were 71, 79, 86 and 97 kDa. Less prominent proteins of approximately 43 and 45 kDa were detected in nuclear extracts. However, antibodies which specifically recognized p43 failed to bind detectably with in situ and isolated host nuclei and nuclear extracts. Expression of p43 was analyzed in host cells infected by newborn larvae irradiated with 60Co. This treatment prevented expression of detectable levels of p43 in resulting muscle larvae, while infected muscle cells displayed typical infected cell characteristics. However, anti-p43 antibodies which recognized multiple ES and nuclear proteins did stain nuclei of irradiated larva-infected cells, albeit at reduced levels. The results raise doubts that p43 is required for induction of the infected cell phenotype. Nevertheless, nuclear antigens recognized by anti-p53 antibodies remain as candidates for influencing this phenotype.
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PMID:Failure to detect Trichinella spiralis p43 in isolated host nuclei and in irradiated larvae of infected muscle cells which express the infected cell phenotype. 787 Jan 27

Infection with hepadnaviruses and exposure to dietary aflatoxin are considered major risk factors in the development of hepatocellular carcinoma (HCC) both in humans and in animals. Recently, a broad range of mutations in the p53 tumor suppressor gene has been reported in human HCCs, predominantly from hepatitis B virus carriers in areas with either high or low levels of exposure to dietary aflatoxin. To determine whether p53 mutations are common to HCCs of hosts infected with related hepadnaviruses with and without treatment with aflatoxin, we studied the occurrence of mutations in the p53 gene in HCCs of ground squirrels and woodchucks with history of infection with ground squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus, respectively. Sequencing of wild type p53 genes from ground squirrels and woodchucks revealed remarkable homology between the two species with only a few amino acid differences in exons 4, 8, and 9. Using direct polymerase chain reaction sequencing, we analyzed the state of the p53 gene (exons 4-9) in 20 HCCs from ground squirrels (2 uninfected, 7 with past, and 11 with ongoing infection with GSHV) and in 11 HCCs from woodchucks persistently infected with woodchuck hepatitis virus. Five GSHV carrier and two uninfected ground squirrels received i.p. administration of aflatoxin B1. We detected only one mutation in the p53 gene of the tested animals. This mutation was located in codon 176 of exon 5 in the HCC of a GSHV-positive ground squirrel treated with aflatoxin. Mutation was caused by a G to T transversion in the second position of the codon, resulting in the replacement of cysteine with phenylalanine, and was accompanied by a tumor-specific loss of heterozygosity. p53 allelic amino acid variation with sequences coding for aspartic acid or asparagine was present in codon 61 in the variable region of exon 4 in both HCCs and nonneoplastic tissues of ground squirrels. In view of the considerably lower apparent rate of mutations in comparison to human HCCs, we suggest a less important role for aflatoxin in the induction of p53 mutations in HCCs of ground squirrels. Alternatively, etiological factors other than p53 mutations may be of greater significance in the development of HCC in ground squirrels and woodchucks.
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PMID:State of the p53 gene in hepatocellular carcinomas of ground squirrels and woodchucks with past and ongoing infection with hepadnaviruses. 792 76


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