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

Overexpression of wild-type p53 in mammalian cells blocks growth. We show here that the overexpression of wild-type human p53 in the fission yeast Schizosaccharomyces pombe also blocks growth, whereas the overexpression of mutant forms of p53 does not. The p53 polypeptide is located in the nucleus and is phosphorylated at both the cdc2 site and the casein kinase II site in S. pombe. A new dominant mutation of p53, resulting in the change of a cysteine to an arginine at amino acid residue 141, was identified. The results presented here demonstrate that S. pombe could provide a simple system for studying the mechanism of action of human p53.
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PMID:Human p53 inhibits growth in Schizosaccharomyces pombe. 154 3

Products of a number of mutant p53 genes bind with high affinity to members of the hsp70 family of chaperonin proteins, whereas wild type p53 lacks this type of association. Examination of the sequences of p53 genes from five different species enabled us to predict domains on p53 which may be involved in the association with hsp70 family members. A synthetic polypeptide (Pro-17-Gly) corresponding to the candidate hsp70 binding domain bound to in vitro translated hsp70 as determined by affinity chromatography and nondenaturing gel mobility shift assays. In addition, the Pro-17-Gly peptide competitively inhibited association between hsp70 and p53, an activity which was determined by immunoprecipitation with anti-p53 monoclonal antibody PAb240. The data indicate that p53 contains a hsp70 binding domain, which is located in a highly conserved region at the amino terminus of the protein, and may participate in the cellular function of wild-type p53 or in the transforming capacity of p53 mutants.
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PMID:hsp70 binds specifically to a peptide derived from the highly conserved domain (I) region of p53. 156 24

Tumor autocrine motility factor (AMF) has been detected in and purified from serum-free conditioned medium of human HT-1080 fibrosarcoma cells. Under nonreducing conditions, AMF migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single band of 55 kDa but under reducing conditions as a band of 64 kDa. Two-dimensional polyacrylamide gel electrophoresis of the purified AMF resolved two groups of polypeptides with isoelectric points of 6.1 and 6.2 (majors), 6.35 and 6.4 (minors). Purified AMF stimulated HT-1080 cell migration in a dose-dependent fashion. The motility stimulation of the fibrosarcoma cells with AMF is associated with the phosphorylation of the AMF receptor, a 78-kDa cell surface glycoprotein (gp78), suggesting protein kinase participation in migratory signal transduction. The gene encoding gp78 was cloned from an HT-1080 fibrosarcoma complementary DNA library. The deduced sequence encodes a polypeptide of 323 amino acids. The nucleotide and predicted amino acid sequence of the gp78 reveals significant homology with the human suppressor/oncogene p53 protein.
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PMID:Purification of human tumor cell autocrine motility factor and molecular cloning of its receptor. 164 92

The regulation of cell proliferation involves p53. A mutant allele of p53, p53-Val135, has been found to be temperature-sensitive for function with separable suppressor and promoter effects on cell proliferation. These opposing suppressor and promoter functions of p53 correlate with two alternative, temperature-sensitive conformations of the p53-Val135 polypeptide.
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PMID:The role of p53 in the normal control of cell proliferation. 195 3

A procedure has been established in Vero cells for the isolation of an intermediate compartment involved in protein transport from the ER to the Golgi apparatus. The two-step subcellular fractionation procedure consists of Percoll followed by Metrizamide gradient centrifugation. Using the previously characterized p53 as a marker protein, the average enrichment factor of the intermediate compartment was 41. The purified fraction displayed a unique polypeptide pattern. It was largely separated from the rough ER proteins ribophorin I, ribophorin II, BIP, and protein disulfide isomerase, as well as from the putative cis-Golgi marker N-acetylglucosamine-1-phosphodiester-alpha-N-acetylglucosaminidase, the second of the two enzymes generating the lysosomal targeting signal mannose-6-phosphate. The first enzyme, N-acetylglucosaminylphosphotransferase, for which previous biochemical evidence had suggested both a pre- and a cis-Golgi localization in other cell types, cofractionated with the cis-Golgi rather than the intermediate compartment in Vero cells. The results suggest that the intermediate compartment defined by p53 has unique properties and does not exhibit typical features of rough ER and cis-Golgi.
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PMID:The isolated ER-Golgi intermediate compartment exhibits properties that are different from ER and cis-Golgi. 200 26

The 55K protein encoded by the adenovirus 2 E1B gene is required for complete cellular transformation and binds the cellular protein p53. Using an in vitro immunoprecipitation assay, we mapped the domains in both 55K and p53 required for the interaction of the two proteins. The domain in p53 mapped to the amino terminal 123 residues. There are several domains in the 495 residue 55K polypeptide which contribute to stable association with p53, with the most essential region mapping between residues 224 and 354. Mutations which prevented 55K-p53 binding were not more defective for transformation than other mutations which did not affect binding.
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PMID:Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55K proteins. 214 4

HeLa cells contain a serine/threonine protein kinase (DNA-PK) that is strongly activated in vitro by low concentrations of double-stranded DNA (dsDNA). Activation was specific for dsDNA; both natural DNAs and synthetic oligonucleotides functioned as kinase activators. The fact that DNA-PK activity was rapidly inhibited by incubation with dsDNA and ATP suggests that DNA-PK activity also may be regulated by autophosphorylation. During gel filtration, DNA-PK activity behaved as a 350-kDa protein, and highly purified DNA-PK contained a dsDNA-binding, 350-kDa polypeptide that was phosphorylated in a dsDNA-dependent manner. We conclude that this 350-kDa polypeptide is likely to be DNA-PK. Previously we showed that the dsDNA-activated kinase phosphorylates two threonines at the N terminus of hsp90 alpha (S. P. Lees-Miller and C. W. Anderson, J. Biol. Chem. 264:17275-17280, 1989). Here we show that DNA-PK also phosphorylates the simian virus 40 large tumor antigen, the mouse tumor-suppressor protein p53, the human Ku autoantigen, and two unidentified HeLa DNA-associated polypeptides of 52 and 110 kDa. Identification of these and other newly identified DNA-binding substrates suggest that the dsDNA-activated kinase may regulate transcription, DNA replication, or cell growth.
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PMID:Human cells contain a DNA-activated protein kinase that phosphorylates simian virus 40 T antigen, mouse p53, and the human Ku autoantigen. 224 67

In normal murine lymphocytes the cellular oncoprotein, p53, exists as two immunologically distinct species which are reciprocally expressed in quiescent (p53-Go) and mitogenically stimulated (p53-G divided by) cells. More recently, we have identified discrete forms of p53, immunologically similar to p53-Go and p53-G divided by, in 3T3 cells transformed by simian virus 40 (SV40). In this report, we demonstrate that immunologically distinct p53 species can also be expressed in vitro, from a single murine p53 cDNA clone. The p53 variants expressed in vitro and in SV40-transformed 3T3 cells have been studied by immunoprecipitation and Western blotting. Immunoprecipitation data indicated that, in their native conformations, the p53 variants react with either the PAb421 or RA3.2C2 monoclonal antibodies, but not with both. When analyzed by Western blotting, however, the denatured proteins were found to react with both monoclonal antibodies. This suggests that the p53 protein is flexible and can fold in alternative conformations so as to expose or mask different epitopes. We propose, therefore, that immunologically distinct p53 species are generated, at least partly, by conformational changes in a single polypeptide species.
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PMID:Evidence that immunological variants of p53 represent alternative protein conformations. 244 54

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.
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PMID:Evaluation of the human T-cell leukemia virus type I seropositivity of blood donors by the particle agglutination inhibition test. 251

Anchorage-independent growth is highly correlated with neoplastic growth in vivo, and the retinoids (vitamin A and its analogs) inhibit this property in a wide variety of oncogenically transformed cells. We report here that retinoic acid-treated Rous sarcoma virus-transformed rat (RR1022) and vole (SR-1T) cells, which show reversible loss of anchorage-independent growth and assume nontransformed morphology, secrete a major 69-kilodalton phosphoprotein (pp69) instead of the 62-kilodalton phosphoprotein (pp62) secreted by their untreated counterparts. As determined by V8 protease mapping and by two-dimensional electrophoretic analysis, this 69-kilodalton polypeptide was indistinguishable from the pp69 released by nontransformed normal rat kidney cells. Neither retinoic acid-treated RR1022 cells nor normal rat kidney cells secreted pp62, and retinoic acid treatment did not have any significant effect on the synthesis, subcellular localization, or phosphokinase activity of pp60src. Furthermore, treatment with retinoic acid did not alter the synthesis of the transformation-specific 53-kilodalton phosphoprotein (p53) and secretion of the transforming growth factors in RR1022 cells. Our studies showed that there is a clear correlation between the release of pp69 or pp62 and the ability of cells to grow in vitro with or without anchorage. This may provide an important clue for elucidating specific biochemical events involved in anchorage regulation of growth.
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PMID:Altered processing of a major secreted phosphoprotein correlates with tumorigenicity in Rous sarcoma virus-transformed mammalian cells. 257 46


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