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 cellular tumor antigen p53 was isolated from mouse neuroblastoma cells and was found in a form not complexed to another protein. The p53 in these cells was stable, turning over about every 10 h. Its methionine-labelled tryptic peptides were very similar to those of the p53 isolated from SV40-transformed mouse cells. The labelled protein was purified from neuroblastoma cells by immunoaffinity using specific monoclonal antibodies and was about 80% radiochemically pure. Furthermore, the purified p53 sedimented in sucrose gradients with a sedimentation coefficient of approximately 8S. This correlated with the sedimentation coefficient of p53 prior to purification, showing that the purified protein retained its native size.
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PMID:Immunoaffinity chromatography of a cellular tumor antigen from mouse neuroblastoma cells. 635 54

The relationship between the expression of a transformation-related cellular-encoded phosphoprotein, p53, and the potential to form distant metastases was investigated in Abelson murine leukemia virus-transformed murine large cell lymphoma sublines of differing metastatic behaviors. Low metastasis RAW117-P and high metastasis RAW117-H10 cells were labeled with 35S-methionine, and several anti-p53 monoclonal antibodies were used to immunoprecipitate p53 from the cell lysates. Using these procedures, similar amounts of p53 were detected in the RAW117-P and -H10 cells. In addition, the expression of 2.0 Kb mRNA containing p53-specific sequences was equivalent in RAW117-P and -H10 cells. The results indicate that p53 expression, although apparently required for neoplastic transformation, is not quantitatively related to metastatic behavior in RAW117 large cell lymphoma cells.
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PMID:The expression of transformation-related protein p53 and p53-containing mRNA in murine RAW117 large cell lymphoma cells of differing metastatic potential. 639 97

A c-DNA clone containing the complete sequence information for the murine p53 protein, from embryonal carcinoma cells, has been isolated. The nucleotide sequence of this clone reveals an open reading frame encoding a protein of 390 amino acids with a molecular weight of 43,364 Da. The NH2-terminal domain of this protein is acidic whereas the carboxyl terminus is rich in basic amino acid residues. These terminal domains are separated by a proline-rich, hydrophobic run of amino acids. Proline comprises approximately 10% of the total amino acid residues. Two tryptic peptides, derived from p53 protein radiolabeled with either methionine or proline, were purified and the position of these labeled residues in the peptide was determined. The positions of three methionine and five proline residues in these two peptides matched the amino acid sequence of the predicted open reading frame determined from the c-DNA clone.
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PMID:The amino acid sequence of murine p53 determined from a c-DNA clone. 640 59

A molecular complex of simian virus 40 large tumor antigen (T-Ag) and p53 cellular protein is present on the surface of simian virus 40-transformed mouse cells. The stability of the association of the two proteins with the cell surface was characterized. Cells were either surface iodinated by the lactoperoxidase technique or metabolically labeled with [35S]methionine, and surface antigens were detected by differential immunoprecipitation with specific antibodies immediately after labeling or after incubation at 37 degrees C. A rapid, concomitant disappearance of T-Ag and p53 from the cell surface was observed. The half-life of iodinated surface T-Ag was less than 30 min, whereas that of [35S]methionine-labeled surface T-Ag was 1 to 2 h. Although T-Ag and p53 were rapidly lost, both were also rapidly replaced on the cell surface, since newly exposed molecules could be detected when cells were reiodinated after a 2-h chase period. Control experiments established that the loss of the surface molecules was not induced by the iodination reaction. The appearance of surface T-Ag was prevented when cellular protein synthesis was inhibited with cycloheximide. The disappearance and replacement of T-Ag and p53 appeared to be energy-independent processes, as neither was inhibited by sodium azide or 2,4-dinitrophenol. Incubation of iodinated cells at 4 degrees C did block the loss of T-Ag and p53. These observations suggest that T-Ag and p53 are coordinately turned over in the plasma membrane. The nature of the association of the T-Ag-p53 complex with the cell surface can best be described as highly dynamic.
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PMID:Dynamic nature of the association of large tumor antigen and p53 cellular protein with the surfaces of simian virus 40-transformed cells. 669 Jul 21

In soluble protein extracts obtained from adenovirus productively infected cells, monoclonal antibodies directed against the early region 1B 58,000-dalton (E1B-58K) protein immunoprecipitated, in addition to this protein, a polypeptide of 25,000 molecular weight. An analysis of tryptic peptides derived from this 25K protein demonstrated that it was unrelated to the E1B-58K protein. The tryptic peptide maps of the 25K protein produced in adenovirus 5 (Ad5)-infected HeLa cells and BHK cells were identical, whereas Ad3-infected HeLa cells produced a different 25K protein. The viral origin of this 25K protein was confirmed by an amino acid sequence determination of five methionine residues in two Ad2 tryptic peptides derived from the 25K protein. The positions of these methionine residues in the 25K protein were compared with the nucleotide sequence of Ad2 and uniquely mapped the gene for this protein to early region 4, subregion 6 of the viral genome. A mutant of Ad5 was obtained (Ad5 dl342) which failed to produce detectable levels of the E1B-58K protein. In HeLa cells infected with this mutant, monoclonal antibodies directed against the E1B-58K protein failed to detect the associated 25K protein. In 293 cells infected with Ad5 dl342, which contain an E1B-58K protein encoded by the integrated adenovirus genome, the mutant produced an E4-25K protein which associated with the E1B-58K protein derived from the integrated genome. Extracts of labeled Ad5 dl342-infected HeLa cells (E1B-58K-) were mixed in vitro with extracts of unlabeled Ad5 wild type-infected HeLa cells or 293 cells (E1B-58K+). When the mixed extracts were incubated with the E1B-58K monoclonal antibody, a labeled E4-25K protein was coimmunoprecipitated. When extracts of Ad5 dl342-infected HeLa cells and uninfected HeLa cells (both E1B-58K-) were mixed, the E1B-58K monoclonal antibody failed to immunoselect the E4-25K protein. These data provide evidence that the E1B-58K antigen is physically associated with an E4-25K protein in productively infected cells. This is the same E1B-58K protein that was previously shown to be associated with the cellular p53 antigen in adenovirus-transformed cells.
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PMID:Adenovirus early region 1B 58,000-dalton tumor antigen is physically associated with an early region 4 25,000-dalton protein in productively infected cells. 669 35

We have developed quantitative radioimmunological solid phase assays for the host protein p53 from mouse cells and from human cells. The first assay, for mouse p53, depends on having two monoclonal antibodies reacting with different determinants on the p53 molecule. With this assay we have shown that SV40-transformed cells have approximately 100-fold more p53 than untransformed mouse cells and that other transformed cells have intermediate levels. Embryonal carcinoma cell lines have approximately 50-fold less p53 than SV40-transformed cells. This is in contrast to the high levels of incorporation of [35S]methionine into p53 in these cells and indicates that metabolic labelling is not a valid approach for measuring p53 levels. The second assay, for human p53, required a different approach and made use of the anti-p53 antibodies detected in the sera of some breast cancer patients. Human tumour cell lines contained amounts of p53 varying from the high level seen in SV40-transformed human fibroblasts down to less than one hundredth of this amount. Normal human cells showed low levels of p53. The data confirm that many, but not all, human tumour cell lines contain more p53 than normal cells.
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PMID:Radioimmunoassay of the cellular protein p53 in mouse and human cell lines. 676 38

A transformation-related protein of M(r) 53,000, designated p53, has been detected in a range of neoplastic cell types of the mouse by using immunoprecipitation of [(35)S]-methionine-labeled cell extracts with mouse antiserum [DeLeo, A. B., Jay, G., Appella, E., DuBois, G. C., Law, L. W. & Old, L. J. (1979) Proc. Natl. Acad. Sci. USA 76, 2420-2424]. We have now prepared a monoclonal antibody to p53 and have used it to study the occurrence and intracellular location of p53 by indirect immunofluorescence assays. In accordance with the results of immunoprecipitation, these tests showed p53 in all 13 transformed mouse cell lines studied. In each case, p53 was found in the nucleus. No p53 was detected in normal mouse fibroblasts, 3T3 cells, bone marrow cells, thymus cells, or embryo cells. A serologically related protein was detected in the nucleus of human cells by monoclonal antibody and was found in both normal and neoplastic cultured cells. Expression of p53 in human cells correlates with the growth characteristics of the culture, high p53 levels being associated with rapid cell proliferation and low p53 levels, with cessation of cell division. Normal and malignant human cells differ, however, with regard to the effect of confluency on p53 expression. Normal kidney epithelium and fetal brain cells, which express high p53 levels during exponential growth, show a prompt decrease in p53 associated with contact inhibition of cell division. Malignant cells, on the other hand, continue to express p53 after confluency and subsequent overgrowth of the monolayers. These results suggest that p53 may be involved in the normal regulation of cell division and that malignant transformation leads to abnormalities in the control of p53 expression.
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PMID:p53 transformation-related protein: detection by monoclonal antibody in mouse and human cells. 694 Jan 83

Dietary folate/methyl deficiency provides a unique model of endogenous hepatocarcinogenesis in which to study progressive alterations in DNA methylation patterns during tumor progression in vivo. Weanling male F344 rats were given a semi-purified diet deficient in the methyl donors choline, methionine and folic acid for a period of 9 weeks. Using a genomic sequencing procedure based on the PCR amplification of bisulfite-modified DNA, the methylation status of individual CpG sites within exons 6 and 7 of the p53 gene in liver samples from control and deficient rats was determined. Treatment of denatured nuclear DNA with sodium bisulfite quantitatively converts all cytosine residues to uracil which are then amplified as thymine in the PCR reaction. In contrast, 5-methylcytosine is resistant to bisulfite deamination under the reaction conditions and is amplified as cytosine. Automated sequencing of bisulfite-modified DNA will then elucidate the methylation status of each cytosine residue within a defined gene sequence. In addition to evaluation of the methylation status of the p53 gene, the relative activity of the DNA methyltransferase was also quantified in nuclear extracts from control and folate/methyl deficient rats. The results indicate that specific 5-methyl cytosines within the hepatic p53 gene from methyl deficient rats are resistant to demethylation despite the diet-induced decrease in S-adenosylmethionine and the increase in cell proliferation associated with this dietary intervention. Progressive demethylation was observed at other methylated cytosine residues in folate/methyl deficient rats after 9 weeks despite a paradoxical increase in DNA methyltransferase activity. The application of this sequence-specific technology will allow the definition of the methylation status of every CpG site within a coding sequence or promoter region and should provide new insights into mechanisms and consequences of methylation dysregulation during progressive multistage carcinogenesis.
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PMID:Differential sensitivity to loss of cytosine methyl groups within the hepatic p53 gene of folate/methyl deficient rats. 758 11

Inappropriate expression of Met, the receptor for hepatocyte growth factor/scatter factor, has been implicated in sarcomagenesis via an autocrine mechanism. Sarcomas occur at high frequency in individuals with Li-Fraumeni syndrome as well as in p53-deficient mice. Here we show that these tumors express high levels of Met. Moreover, late passage fibroblast cell lines established from p53-deficient animals overexpress Met and can be tumorigenic in athymic nude mice, suggesting that progression occurs in vitro. The tumor explants display increased hepatocyte growth factor/scatter factor expression and Met turnover, indicating that autocrine Met activation contributes to tumor progression. Thus, the loss of wild-type p53 appears to greatly enhance the opportunity for inappropriate Met expression. Loss of p53 function does not by itself cause transformation, but inappropriate Met expression may be an important factor in sarcomagenesis.
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PMID:Met proto-oncogene product is overexpressed in tumors of p53-deficient mice and tumors of Li-Fraumeni patients. 772 66

Transcripts coding for transcription factors (RB, P53, FOS, MYC, MYB, ERBA, REL), growth factors (FGF1, FGF2, INT2, TGFA, TGFB, PDGF, IGF1, IGF2), interleukins, (IL1, IL2, IL3, IL4, IL6, TNF), growth-factor receptors or cytosolic protein kinases (RAF, PIM, FES, MET, SRC, ROS, TRK, KIT, CSFR, IGFR, PDGFR, EGFR, NEU) were quantified in cultured human mammary fibroblasts from normal tissues, benign tumours, carcinomas and post-radiation fibrosis lesions by slot-blot autoradiography and image analysis. The effects of a differentiating agent (cholera toxin) and of a tumour promoter (12-O-tetradecanoyl-phorbol-13-acetate) were also examined. The drugs modulated the levels of the anti-oncogene transcripts (RB, P53) and of ERBA, REL, RAF, MET, ROS, TRK, CSFR, EGFR, NEU, FGF1, INT2, IGF1, IL1, IL2, IL4 and IL6. Apart from this variation, there were multiple differences in gene expression among normal and pathological cells (concerning all but P53, TGFB and interleukin transcripts) and between sub-types defined by the presence of alpha-sm-actin (myofibroblasts) or EDB-fibronectin (RAF, ROS, FES, KIT, IGFR, NEU, INT2, TGFB, PDGF, IGFs, ILs). It appears, therefore, that mammary stroma progress irreversibly along with the epithelium during tumoral development, and that breast cancer is not only a multi-gene but also a multi-tissue phenotype.
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PMID:Quantitative variation of proto-oncogene and cytokine gene expression in isolated breast fibroblasts. 776 44


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