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)

Simian virus 40 (SV40) is a small, DNA-containing tumour virus. One of its gene products, the large tumour antigen (T-ag), is essential for both viral replication and cell transformation. SV40 T-ag can be considered a dual oncogene protein; it is a composite transforming protein that provides distinct functions at different subcellular locations. In addition to its roles in virus replication, T-ag exerts numerous effects on host cells. Those cellular effects reflect viral stimulation of host cell entry into S phase. Numerous chemical modifications have been ascribed to T-ag. They might be involved in defining subpopulations of T-ag that are, in turn, responsible for mediating various T-ag biochemical functions. The T-ag polypeptide, 90,000-100,000 in molecular weight, appears to contain multiple, discrete functional domains; several biological activities have been assigned to relatively small defined regions of the molecule. The cellular progenitors of the T-ag biochemical activities are not obvious. A cellular protein, p53, thought to be involved in regulation of cell proliferation, becomes complexed with T-ag in transformed cells and is stabilized. The interaction of T-ag with this cellular substrate may play an important part in SV40 transformation. T-ag and T-ag/p53 complexes are localized in both the nucleus and plasma membrane of transformed cells. T-ag is transported to the nucleus because of a 7-residue nuclear transport signal contained within its primary sequence. Its migration to the membrane is by an unknown pathway. Only a minor fraction of the total cellular T-ag is present at the cell surface. Both amino and carboxy termini of the T-ag polypeptide are exposed on the extracellular face of the cell. Nuclear and membrane T-ag are structurally very similar, although a portion of membrane T-ag is acylated and nuclear T-ag is not. The nuclear and membrane forms of T-ag apparently provide separate and complementary functions necessary for cell transformation. Nuclear T-ag is important in immortalizing primary cells and membrane T-ag may mediate more pronounced morphological changes. A model is presented, postulating how the two forms of T-ag might cooperate to mediate phenotypic transformation.
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PMID:SV40 large T-antigen: dual oncogene. 302 25

SV40 large T antigen is phosphorylated at up to ten different amino acids clustered in an N-terminal and a C-terminal part of the polypeptide chain. The N-terminal phosphorylated residues include Ser 123 and Thr 124. We have analyzed the oligomerization, the complex formation with the cellular oncoprotein p53 and the DNA-binding properties of T antigen from two different SV40 transformed cell lines which have either an amino acid exchange at Ser 123 to Phe (W7) or Thr 124 to Ile (D29). In comparison to wild-type T antigen both mutant T antigens have a slightly reduced binding affinity for both binding sites, I and II, of SV40 DNA. Phosphorylation at both residues of T antigen is not essential for formation of the complex with p53. Only the phosphorylation at Thr 124 seems to be critical for the formation of high molecular mass oligomers. Our data support the hypothesis that the oligomerization of T antigen seems to be implicated in viral DNA replication.
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PMID:The phosphorylation at Thr 124 of simian virus 40 large T antigen is crucial for its oligomerization. 304 Apr 70

The protein p53 is capable of participating in neoplastic transformation and can form specific complexes with the large-T antigen of simian virus 40 (SV40). This interaction probably results in the stabilization of p53 (refs 7,8) and may contribute to SV40-mediated transformation. Several non-SV40-transformed cells also exhibit a stabilized p53 which is present in elevated levels. Recently, this stabilization was shown to coincide with the ability to precipitate a polypeptide (p68) of relative molecular mass (Mr) 68,000-70,000 by anti-p53 monoclonal antibodies. We now report that this co-precipitation indeed represents a specific complex between the two proteins; the complex sediments on a sucrose gradient as a relatively broad peak of 10-14S and can be dissociated in vitro. Furthermore, p68 is the HSP70 heat shock protein cognate, found in elevated levels in a p53-overproducing cell line. On heat-shock treatment of such overproducers, p53 also forms a complex with the related highly inducible HSP68.
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PMID:Specific interaction between the p53 cellular tumour antigen and major heat shock proteins. 351 22

Three clones for the human tumor antigen p53 were isolated from a cDNA library prepared from A431 cells. One of these clones, pR4-2, contains the entire coding region for human p53. This clone directs the synthesis of a polypeptide with the correct molecular weight and immunological epitopes of an authentic p53 molecule in an in vitro transcription-translation reaction. Although the pR4-2 clone contains the coding region for p53, it is not a full-length copy of the human p53 mRNA. Northern analysis showed that the p53 mRNA is approximately 2,500 nucleotides long, whereas the pR4-2 insert is only 1,760 base pairs in length. Analysis of the DNA sequence of this clone suggests that the human p53 polypeptide has 393 amino acids. We compared the predicted amino acid sequence of the pR4-2 clone with similar clones for the mouse p53 and found long regions of amino acid homology between these two molecules.
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PMID:Molecular cloning and in vitro expression of a cDNA clone for human cellular tumor antigen p53. 389 33

A 2.5-kb cDNA clone for human p53 tumor antigen has been isolated. This clone contains the entire coding region including 135 bp upstream of the first ATG. Comparison of the nucleotide sequence of human p53 and mouse p53 demonstrates that the first ATG in human p53 corresponds to the second ATG (codon No. 4) in mouse p53. The human p53 comprises 393 residues and is longer than the mouse p53 due to six additional codons present at the region corresponding to exon 4 of the mouse p53 gene. The DNA sequence homology between the coding regions of mouse and human p53 is 81% and the conservation of homology is not equally distributed along the molecule. When inserted into SV40-based expression vectors the human p53 cDNA successfully directs the production of a polypeptide with an apparent mol. wt. of 55 kd which can be precipitated by monoclonal antibodies to p53.
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PMID:Human p53 cellular tumor antigen: cDNA sequence and expression in COS cells. 400 16

Purified virions of tick-borne encephalitis (TBE) virus contain 3 proteins, V1, V2 and V3, with molecular weights of 8 000, 13 000 and 53 000 daltons, respectively. Seven virus-specific polypeptides were revealed in TBE-virus infected continuous pig embryo kidney cells, namely p93-96, p79, p69, p53, p47, p16 and p13 (pN designating polypeptide with a mol wt of N X 1 000 daltons). Proteins p93-96, p69, p53, p47 and p13 corresponded by their mol wt to proteins NV5, NV4, V3 and V2 (NV1 1/2) of mosquito-borne flaviviruses. Protein p79, designated NV4 1/2, and protein p16 (the only virus-specific protein inhibited by hypertonic NaCl concentrations), had no analogues among proteins of mosquito-borne flaviviruses. The possibility of a cellular origin of protein p47 (NV3) is discussed.
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PMID:Synthesis of virus-specific proteins in tick-borne encephalitis virus-infected pig embryo kidney cells. 610 57

The antigenic structure of simian virus 40 (SV40) large tumor antigen (T-ag) in the plasma membranes of SV40-transformed mouse cells and SV40-infected monkey cells was characterized as a step toward defining possible biological function(s). Wild-type SV40, as well as a deletion mutant of SV40 (dl1263) which codes for a truncated T-ag with an altered carboxy terminus, was used to infect permissive cells. Members of a series of monoclonal antibodies directed against antigenic determinants on either the amino or the carboxy terminus of the T-ag polypeptide were able to precipitate surface T-ag (as well as nuclear T-ag) from both SV40-transformed and SV40-infected cells. Cellular protein p53 was coprecipitated with T-ag by all T-ag-reactive reagents from the surface and nucleus of SV40-transformed cells. In contrast, T-ag, but not T-ag-p53 complex, was recovered from the surface of SV40-infected cells. These results confirm that nuclear T-ag and surface T-ag are highly related molecules and that a complex of SV40 T-ag and p53 is present at the surface of SV40-transformed cells. Detectable levels of such a complex do not appear to be present on SV40-infected cells. Both the carboxy and amino termini of T-ag are exposed on the surfaces of SV40-transformed and -infected cells. The possible relevance of the presence of a T-ag-p53 complex on the surface of SV40-transformed cells and its absence from SV40-infected cells is considered.
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PMID:Antigenic structure of simian virus 40 large tumor antigen and association with cellular protein p53 on the surfaces of simian virus 40-infected and -transformed cells. 620 66

The cellular tumour antigen p53 is implicated in the transformation process. To compare p53 from transformed cells and their normal counterparts in detail, and so to identify any structural differences that might alter p53 function, requires information on the primary structure of the protein. By making use of immunochemical techniques we have been able to purify nanomole amounts of p53. This was sufficient, using high sensitivity automated gas-phase sequencing techniques to determine the amino acid sequence of two tryptic peptides from p53. Their sequences agree completely with the predicted polypeptide sequence derived from a cloned cDNA for p53 mRNA and provide the first data on the amino acid sequence of p53. A combination of the high sensitivity amino acid sequencing procedures used here and cDNA sequence analysis should provide the complete amino acid sequence of p53.
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PMID:Purification and partial amino acid sequence analysis of the cellular tumour antigen, p53, from mouse SV40-transformed cells. 631 11

A cDNA clone for human p53 cellular tumor antigen has been isolated and characterized. This clone contains the complete 3'-untranslated region and most of the open reading frame for the protein. Nucleotide sequence analysis revealed that p53 mRNA contains an Alu repeat in the 3'-untranslated region. Hybridization selection experiments showed this clone was capable of selectively binding p53 mRNA. In vitro translation of SV80 mRNA resulted in the synthesis of two immunoreactive p53 polypeptide species. Northern blot analysis showed that human p53 mRNA was 2.8 kb in length and was present in cell lines containing high and low levels of p53 protein. There appears to be only a single p53 gene in human cells and Southern blot analysis demonstrated no major genomic rearrangements or amplification of the p53 gene in the transformed cell lines examined.
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PMID:Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene. 639 87

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


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