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)

We have investigated the role of the p53 gene in oncogenesis in vivo by generating transgenic mice carrying murine p53 genomic fragments isolated from a mouse Friend erythroleukemia cell line or BALB/c mouse liver DNA. Elevated levels of p53 mRNA were detected in several tissues of two transgenic lines tested. Increased levels of p53 protein were also detected in most of the tissues analyzed by Western blotting (immunoblotting). Because both transgenes encoded p53 proteins that were antigenically distinct from wild-type p53, it was possible to demonstrate that overexpression of the p53 protein was mostly, if not entirely, due to the expression of the transgenes. Neoplasms developed in 20% of the transgenic mice, with a high incidence of lung adenocarcinomas, osteosarcomas, and lymphomas. Tissues such as ovaries that expressed the transgene at high levels were not at higher risk of malignant transformation than tissues expressing p53 protein at much lower levels. The long latent period and low penetrance suggest that overexpression of p53 alone is not sufficient to induce malignancies and that additional events are required. These observations provide direct evidence that mutant alleles of the p53 oncogene have oncogenic potential in vivo and that different cell types show intrinsic differences in susceptibility to malignant transformation by p53. Since recent data suggest that p53 may be a recessive oncogene, it is possible that the elevated tumor incidence results from functional inactivation of endogenous p53 by overexpression of the mutant transgene. The high incidence of lung and bone tumors suggests that p53 transgenic mice may provide a useful model to investigate the molecular events that underlie these malignancies in humans.
Mol Cell Biol 1989 Sep
PMID:High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene. 247 68

A hybrid clone was developed by the fusion of a pluripotent mouse teratocarcinoma cell line PCC-4 AzaR to the Zajdela ascitic hepatoma (ZAH) of rat origin. This hybrid cell line, F2231A, possessed a predominantly teratocarcinoma morphology with a large nucleus and prominent nucleoli, and grew in nests. F2231A cells formed undifferentiated tumours in irradiated Sv/129 mice. It formed aggregates when subcultured at high densities in bacteriological Petri dishes. The hybrid cell line differentiated in response to retinoic acid and also underwent spontaneous differentiation upon overgrowth. Karyological analysis showed the presence of several rat chromosomes in the hybrid and upon isozyme analysis it was found that only the rat variant of the X-linked enzyme HGPRT was expressed. Analysis of the genomic DNA with a cloned probe, specific for rat repetitive sequences, gave strong positive signals in the hepatoma parent and F2231A cells while the parental embryonal carcinoma (EC) cells were negative. The hybrid cell line, like the PCC-4 cells, expressed the SSEA-1 surface marker but not SSEA-3, intercellular fibronectin and EGF receptors. Upon differentiation of F2231A cells there was a loss of expression of SSEA-1. The mRNA for alpha-fetoprotein was expressed by the hybrid cell line and in this respect it resembled the hepatoma parent. Albumin mRNA was not detectable in the hybrid cell line. The mRNA for the transformation-related protein, p53, was expressed at a high level in F2231A cells. The hybrid cell line F2231A retained several of the biochemical and immunological properties of the teratocarcinoma cells.
Cell Differ Dev 1989 Sep
PMID:A malignant, stem cell-like somatic hybrid between a mouse teratocarcinoma and a rat ascitic hepatoma is differentiation competent. 247 69

In the HTLV-I seroscreening of blood donor sera by gelatin particle agglutination (PA), more than 50% (55.6%) of the PA-positive sera were negative by immunofluorescence assay (IF). However, when donors were divided into age groups, there were increasing numbers of IF-positive/PA-positive donors with age. Among the PA-positive donors in the 50-64 age group, 65.9% were IF-positive compared to 16.0% in the 16-19 age group. The serological specificities of the IF-negative/PA-positive specimens were tested by using a newly developed PA inhibition (PAI) test. The HTLV-I specificity of the PAI test was confirmed by the observation that agglutinations with anti-HTLV-I p19 and gp21 monoclonal antibodies as well as IF-positive sera were specifically inhibited with HTLV-I preparations or HTLV-I-positive cell extracts and not with HTLV-I-negative cell extracts. Sixty of the 104 specimens collected randomly from the IF-negative/PA-positive donors were PAI-positive. The majority (80%) of such PAI-positive sera showed more than two bands of HTLV-I gag-encoded polypeptide, p19, p24, p28 and p53 on Western blotting. Some of the PAI-positive sera were also positive by enzyme immunoassay. These results indicate that at least some of the IF-negative/PA-positive donors possess HTLV-I-specific antibody and may be potential HTLV-I carriers who will become IF-positive at a later age.
Jpn J Cancer Res 1989 Sep
PMID:Evaluation of the human T-cell leukemia virus type I seropositivity of blood donors by the particle agglutination inhibition test. 251

It is known that large T antigen, the regulatory protein encoded by Simian virus 40 (SV40), forms tight complexes with the cellular p53 protein in SV40-transformed rodent cells. Using immunoaffinity procedures we have purified large T antigen and, in separate experiments, the cellular p53 protein. The two proteins formed complexes in vitro which bound well to double-stranded DNA fragments although in a sequence-unspecific manner. Free, uncomplexed T antigen readily converted double-stranded DNA into a single-stranded form whereas in-vitro-formed p53-T-antigen complexes were inactive in this reaction. We conclude that one function of p53 in SV40-transformed mouse cells could be the inhibition of the replication initiating activity of T antigen.
Eur J Biochem 1989 Sep 01
PMID:Effects of the cellular p53 protein on Simian-virus-40-T-antigen-catalyzed DNA unwinding in vitro. 255 Feb 25

Antibody spectra to individual proteins of human immunodeficiency virus (HIV) in 74 seropositive serum samples collected in the USSR and 65 serum samples collected in Britain were studied by immunoblotting techniques. Most of the sera belonged to clinically healthy persons, some of the sera collected in Britain contained specific IgM antibodies. The results were evaluated qualitatively and quantitatively. In the former case the study of samples collected both in the USSR and in Britain yielded similar results which also coincided with the data of literature regarding asymptomatic virus carriers: very high content of antibodies to protein gp41 and sufficiently high content of antibodies to protein p24 were registered in all sera. But the quantitative evaluation of the results of this investigation revealed differences between serum samples collected in these two countries. The main feature of sera collected in the USSR was their noticeably greater reactivity with respect to the products of HIV gene gag: proteins p24, p53 and p22. The explanations of this phenomenon are discussed.
Zh Mikrobiol Epidemiol Immunobiol 1989 Sep
PMID:[A comparison of the spectra of antibodies to individual proteins of the human immunodeficiency virus in seropositive sera collected in the territories of the USSR and England]. 258 79

The expression of three growth-regulated protooncogenes, c-myc, c-myb, and p53, and the S-phase-specific histone H3 gene, was compared in bone marrow cells from multiple myeloma patients and normal controls by measuring the amount of specific RNA by Northern blot analysis. Four samples contained at least 72% of myeloma cells, one sample 43%, and one 11%. Expression of the protooncogenes was similar in normal and myeloma bone marrow cells, whereas that of histone H3 gene was significantly reduced (between 10 and 15 times) in samples containing at least 43% of malignant plasma cells and not detectable in those containing more than 72% of neoplastic cells. Protooncogene levels of expression were compared to those of the H3 gene to distinguish the increased expression of a growth-regulated gene due to a true deregulation from overexpression reflecting solely an increase in the fraction of cycling cells. The ratios of expression of protooncogenes to histone H3 were markedly increased in multiple myeloma cells; the highest ratios were found in the patients with the highest number of malignant plasma cells. These results suggest that the expression of three growth-regulated oncogenes (c-myc, c-myb, p53) is altered in myelomatous plasma cells.
Cancer Res 1989 Sep 01
PMID:Altered expression of growth-regulated protooncogenes in human malignant plasma cells. 266 53

We have investigated the biochemical properties of Xenopus laevis p53. With an in vitro binding assay, we can detect a specific association between X. laevis p53 and simian virus 40 large T antigen. Furthermore, X. laevis p53 expressed in monkey COS cells is stably associated with this viral antigen. Like mammalian p53, X. laevis p53 in complex with simian virus 40 large T antigen exhibits a 20-fold increase of its half-life. On the other hand, X. laevis p53 is unable to associate either in vivo or in vitro with adenovirus type 5 E1B 55-kilodalton protein. We show by an immunological technique that X. laevis p53 forms specific complexes with mammalian hsp72 and hsp73 heat shock proteins only at a temperature well above the optimal growth temperature for X. laevis. Our results suggest that the protein-binding properties of p53 are closely related to the functional activity of the protein.
J Virol 1989 Sep
PMID:Evolutionary conservation of the biochemical properties of p53: specific interaction of Xenopus laevis p53 with simian virus 40 large T antigen and mammalian heat shock proteins 70. 266 61

We analysed large T antigen expression and metabolic stabilisation of the cellular protein p53 in cells of a matched pair of SV40 tsA mutant (tsA58) N-type or A-type transformants, respectively. At the permissive growth temperature (32 degrees C), cells of both transformants, like SV40 wild-type transformed cells, were phenotypically transformed and expressed large T antigen, as well as metabolically stable p53 (both complexed and free p53). At the nonpermissive growth temperature (39 degrees C), cells of the N-type transformant reverted to a normal phenotype, whereas cells of the A-type transformant still displayed a transformed phenotype. Under these growth conditions, the mutant large T antigens in both cell types were no longer able to complex p53 (both in vivo and in vitro), but the metabolic stabilities of the free p53 in these cells correlated with their phenotypes: p53 in cells of the N-type transformant was rapidly degraded, whereas it was metabolically stable in cells of the A-type transformant. This difference in p53 stability correlated with an in vivo functional difference between the mutant large T antigens at the nonpermissive growth temperature: large T antigen in cells of the N-type transformant no longer stably associated with the cellular chromatin and the nuclear matrix, but accumulated in the nucleoplasm. In contrast, large T antigen in cells of the A-type transformant at least partially had retained this ability. Maintenance of SV40 cell transformation thus seems to require both a functional large T antigen and a metabolically stabilised p53.
Oncogene 1989 Sep
PMID:Cooperation of SV40 large T antigen and the cellular protein p53 in maintenance of cell transformation. 267 54

The viral oncoprotein of simian virus 40, large T antigen (T-ag), is essential for viral replication and cellular transformation. To understand the mechanisms by which T-ag mediates its multifunctional properties, it is important to identify the cellular targets with which it interacts. A cellular protein of 73 kilodaltons (p73) which specifically associates with T-ag in simian virus 40-transformed BALB/c 3T3E cells has been identified. The binding of p73 to T-ag was demonstrated by coimmunoprecipitation analyses using polyclonal and monoclonal antibodies specific for T-ag. The interaction of p73 with T-ag was independent of T-ag complex formation with the cellular protein p53. Partial V8 protease cleavage maps for p73 and the cellular heat shock protein hsp70 were identical. Immunoblot analyses indicated that p73 complexed to T-ag was antigenically related to hsp70. T-ag deletion mutants were constructed that remove internal, amino-terminal, and carboxy-terminal sequences. These mutants mapped the p73 binding domain to the amino terminus of T-ag. The specific dissociation of p73 from the p73/T-ag complex was mediated by ATP; GTP, CTP, and UTP were also utilized as substrates. These characteristics suggest that p73 may be a member of the hsp70 family of heat shock proteins. The biologic significance of p73/T-ag complex formation has yet to be determined.
J Virol 1989 Sep
PMID:Association of a cellular heat shock protein with simian virus 40 large T antigen in transformed cells. 276 Sep 86

Molecular mechanisms responsible for the clinical progression of chronic myelocytic leukemia to its accelerated phase or to blast crisis have not been defined. We found alterations of the p53 gene (p53 is a 53-kDa nuclear protein) including deletions and rearrangements in 8 of 34 patients in blast crisis and 1 of 4 patients in the accelerated phase, but in only 1 of 38 patients in the chronic phase of chronic myelocytic leukemia. Only two other examples of p53 gene alterations were found among 203 patients with hematologic malignancies and solid tumors. Transcripts of the p53 gene were uniformly found in chronic-phase cells, but gene expression was variable in blast crisis, and transcripts were reduced or undetectable in 10 of 16 patients. Heterogeneous alterations in the structure and expression of the p53 gene appear to be relatively frequent in blast crisis and may be involved in the evolution of disease.
Proc Natl Acad Sci U S A 1989 Sep
PMID:Alterations in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia. 277 57


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