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

Crosslinking of membrane immunoglobulin (mIg) on B cells induces two signal transduction pathways: protein tyrosine phosphorylation and phosphoinositide turnover. A panel of murine and human B cell-lines, representing different stages of B cell development, was examined for the presence of anti-immunoglobulin-induced protein tyrosine phosphorylation. Of 10 B cell lines examined, only one, the human Raji cell line, had no detectably induced protein tyrosine phosphorylation. The pattern of proteins that were phosphorylated on tyrosine in response to mIg crosslinking differed somewhat in cell lines representing different stages of B cell development. Differences in the levels of constitutive phosphorylation of proteins were also observed between the cell lines. The identity of the tyrosine kinase(s) activated by membrane immunoglobulin ligation is not known. However, members of the src family of intracellular tyrosine kinases have been implicated as signal transduction molecules. As the tyrosine phosphorylation of proteins is a general phenomenon of signal transduction by membrane immunoglobulin, the tyrosine kinase(s) activated by it might be expected to be present in all cell lines in which the tyrosine phosphorylation signalling occurs. Therefore we examined these B cells for expression of mRNAs encoding the eight known src-like tyrosine kinases. Surprisingly, all eight kinase mRNAs were expressed in at least some of the B cell lines examined. The expression pattern of the fyn, hck, and lck genes suggests that expression of these kinases may be developmentally regulated in the B cell lineage. Three of the kinases, p55blk, p53/p56lyn and p60src, were detected in all 10 B cell lines. Whereas the src gene shows a ubiquitous pattern of expression, the expression of the blk and lyn genes is mostly restricted to cells of hematopoietic origin, and more especially B lymphoid cells. Thus, p55blk and p53/p56lyn may be particularly good candidates for the membrane immunoglobulin-activated tyrosine kinase.
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PMID:Examination of B lymphoid cell lines for membrane immunoglobulin-stimulated tyrosine phosphorylation and src-family tyrosine kinase mRNA expression. 137 35

EBV/C3d receptor (CR2) interacts with the p53 anti-oncoprotein expressed in the human B lymphoma cells, Raji but not in normal B cells, and with the p68 calcium-binding protein, expressed in normal B lymphocytes but not in transformed B lymphocytes. To characterize the CR2 domain interacting with these two intracellular proteins, we synthesized a 34-amino acid peptide, pep34, corresponding to its intracytoplasmic carboxy-terminal domain and analyzed its binding and antigenic properties. Binding of 125I-labeled p53 or 125I-labeled p68 on immobilized pep34 was specific, additive, and totally inhibited by unlabeled p53 or p68, respectively, but not by unlabeled p68 or p53, respectively. Antigenic properties of pep34 were analyzed by immunizing rabbits with particle-bound pep34. Polyclonal anti-pep34 Ab carried anti-CR2 specificities that recognized only the intracellular domain of CR2. In addition, anti-pep34 Ab also carried anti-p53 or anti-p68 specificities. Anti-p53 or anti-p68 specificities were not due to putative common structural or conformational antigenic determinants between the pep34 synthetic peptide and the p68 or p53 proteins. These anti-p53 and anti-p68 specificities were identified as anti-idiotypic anti-CR2 Ab mimicking either p53 or p68 binding sites of CR2. These data clearly establish that despite its short length, the intracytoplasmic C-terminal tail of CR2 is involved in direct protein-protein interactions with the two intracellular regulatory proteins, p53 and p68. An additional feature of these data is the demonstration that particle-bound pep34 triggered "in vivo" anti-Id Ab restricted to either p53 or p68 specificities.
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PMID:EBV/C3d receptor (CR2) interacts by its intracytoplasmic carboxy-terminal domain and two distinct binding sites with the p53 anti-oncoprotein and the p68 calcium-binding protein. 143 Nov 1

The nuclear phosphoprotein p53 is an important regulator of cell proliferation in normal cells. Interestingly, the gene encoding p53 has usually undergone mutations in a wide range of tumor types. Recent studies of the p53 gene in Burkitt's lymphomas have demonstrated that mutations are extremely common, and in fact it is rare that both alleles of the p53 gene in these tumors are not inactivated by mutation or deletion. We present here genetic data regarding the status of the p53 gene in the Burkitt lymphoma cell line, Raji. As is typical for this type of tumor, both alleles have undergone point mutations. Further, statistical analysis of available data from a large number of Burkitt's lymphomas indicates an apparent tumor-specific distribution of p53 mutations. The possibility that specific mutations of the p53 gene may be important for different tumor types is discussed.
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PMID:p53 mutations in Raji cells: characterization and localization relative to other Burkitt's lymphomas. 143 44

The nuclear protein p53 has been reported to be associated with cell transformation and/or proliferation so that the study of p53 expression in human malignancy has potentially important clinical implications. We have analyzed the p53 expression in mitogen-stimulated and nonstimulated human lymphocytes, in several human leukemia cell lines (Molt-4, Raji, Daudi, HL-60, KG-1, K562 and U937) and in fresh bone marrow (BM) cells. Simultaneous differential staining of p53 (identified by a FITC-labeled monoclonal antibody) versus DNA (stained with propidium iodide, PI), followed by bivariate analysis with flow cytometry (FCM) made it possible to evaluate p53 expression with respect to cell position during the cell cycle. The data show that in stimulated lymphocytes p53 is progressively accumulated during the G1, S and G2-phases, while in non-stimulated conditions most cells are remaining in G0/G1 and express p53 to a lesser degree. This suggests that expression of p53 is more correlated with cell growth than with entrance into (or progression through particular phases of) the cell cycle. Cells from acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma cell lines express elevated levels of p53, while all examined human acute myeloid leukemia cell lines synthesize negligible p53 protein. Understanding the variations in p53 expression in different types of human leukemia may provide some insight into the biologic roles of p53 in normal and malignant cells.
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PMID:Expression of p53 protein during the cell cycle measured by flow cytometry in human leukemia. 214 May 91

Epstein-Barr virus and the C3d fragment of the third component of complement are specific extracellular ligands for complement receptor type 2 (CR2). However, intracellular proteins that react specifically with CR2 and are involved in post-membrane signals remain unknown. We recently prepared polyclonal anti-idiotypic anti-CR2 antibodies (Ab2) by using the highly purified CR2 molecule as original immunogen. We showed that Ab2 contained anti-idiotypic specificities that mimicked extracellular domains of CR2 and detected two distinct binding sites on CR2 for its specific extracellular ligands, Epstein-Barr virus and C3d. We postulated that Ab2 might also contain specificities that could mimic intracellular domains of CR2. Here we report that Ab2, which did not react with Raji B-lymphoma cell surface components, detected specifically, among all components solubilized from Raji cell membranes, a single intracellular membrane protein of apparent molecular mass of 53 kDa. This protein was identified as the p53 cellular antioncogene-encoded membrane phosphoprotein by analyzing its antigenic properties with Pab1801, a monoclonal anti-p53 antibody, and by comparing its biochemical properties with those of p53. Additionally, solubilized and purified CR2 bound to solubilized p53 immobilized on Pab1801-Sepharose. p53, like CR2, was localized only in purified plasma membranes and nuclei of Raji cells. These data suggest strongly that p53, a cellular antioncogene-encoded phosphoprotein, reacted specifically with CR2 in Raji membranes. This interaction may represent one of the important steps through which CR2 could be involved in human B-lymphocyte proliferation and transformation.
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PMID:Epstein-Barr virus/complement fragment C3d receptor (CR2) reacts with p53, a cellular antioncogene-encoded membrane phosphoprotein: detection by polyclonal anti-idiotypic anti-CR2 antibodies. 255 14

To gain insight into how transcription of the human p53 oncogene is controlled, we characterized the regulatory regions of the gene. A 3.8-kilobase-pair (kbp) EcoRI restriction fragment encompassing the 5' end of the human p53 gene, as well as subfragments generated by restriction digests, was cloned upstream of the Escherichia coli chloramphenicol acetyltransferase (CAT) gene and CAT activity was assayed in extracts of transfected cells. Two types of CAT vectors were used: Epstein-Barr virus oriP-derived constructs that were stably introduced into the human cell lines K562, Raji, and HL-60, and pSV0-CAT-derived constructs that were transiently introduced into the monkey cell line COS. By this approach we have identified two promoters for the human p53 gene. One promoter, p53P1, is located 100-250 bp upstream of the 218-bp noncoding first exon; a second, stronger promoter, p53P2, maps within the first intron. CAT activity and expression of CAT RNA indicate that p53P2 functions up to 50-fold more efficiently than p53P1. We conclude that the expression of the human p53 gene may be controlled by two promoters and that differential regulation of these promoters may play an important role in the altered expression of the gene in both normal and transformed cells.
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PMID:Human p53 oncogene contains one promoter upstream of exon 1 and a second, stronger promoter within intron 1. 283 31

We have recently reported that the c-myc protein may promote cellular DNA replication by binding to the origin of DNA replication (ori) and that an origin of human DNA replication which can autonomously replicate in human cells was cloned as a binding sequence of c-myc protein (Iguchi-Ariga et al., 1987). Here we report that cellular tumor antigen p53 may also participate in cellular DNA replication and another origin of DNA replication was cloned as a possible p53-binding sequence. The sequence could autonomously replicate in Raji cells which express p53 at a high level but not in HL-60 cells in which the coding gene for p53 is largely deleted. Little homology of the sequences was found between c-myc protein-binding ori and p53-binding ori. This suggests that c-myc protein and p53 may independently recognize different ori in chromosomal DNA.
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PMID:Cloning of the p53-dependent origin of cellular DNA replication. 297 68

To answer the question whether the level of p53 expression also reflects the status of a cell, with reference to transformation and genome stability, we have examined, by immunocytochemistry, the presence of p53 protein in a number of cell types including human diploid cells, Chinese hamster embryonal cells at different passages and gene amplified and/or transformed Chinese hamster cell lines. Primary human fibroblasts at early passage (LEO) and an established, non transformed, Chinese hamster cell line at early passage (CHEF/18) did not show any detectable p53 expression, either nuclear or cytoplasmic. All transformed human (Raji) and Chinese hamster cell lines (CHO, V79, V79/B7) showed a nuclear expression of p53, although at different intensities. Two cell lines selected from V79/B7 for their resistance to phosphonacetyl-L-aspartate or methotrexate and previously shown to bear gene amplification, showed p53 expression. In PALA L cells p53 expression was nuclear as in other positive cell lines tested, while in MTX M cells it was cytoplasmic. CHEF/18 cells at late passage in culture showed the typical behaviour of transformed cells and p53 was detected in several cells. Moreover, when transformed CHO cells were treated with compounds known to induce reverse transformation, both the disappearance of hallmarks of transformed phenotype and p53 reduction were observed. These results indicate a strong association within the same cell type between p53 expression and transformed status.
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PMID:p53 expression in normal versus transformed mammalian cells. 758 48

The expression of the p53 tumor suppressor gene in ten human cell lines (nine cancers and one normal) was studied using reverse transcription, polymerase chain reaction (PCR) and direct sequencing. Using P53U and P53D primers for amplifying a 371-base pair (bp) target fragment spanning exons 7-10 of p53 cDNA, normal-sized PCR products were amplified from 9 cell lines but not from the Hep3B hepatocellular carcinoma (HCC) cell line. An additional larger band (504 bp) was observed for the Molt-4 T-lymphoblastic leukemia cell line. Employing P531 and P53D primers which flank a 76-bp p53 cDNA fragment, 76 bp as well as 209 bp products were generated by PCR of Molt-4 cDNA. Direct sequencing of the 504 bp and 209 bp bands confirmed the presence of a 133 bp insertion between exons 9 and 10 in the aberrant transcript. This insertion was homologous to a 130-bp sequence within the wild-type p53 intron 9, except for 2 point mutations and 3 base insertions. Sequencing of P53U/P53D PCR products of Molt-4 genomic DNA revealed an 8 bp deletion just downstream to the 133 bp insertion, creating a novel donor splicing site within intron 9. This site, coupled with an inherent acceptor splicing site just upstream to the 133 bp insertion, suggests that the 133 bp stretch represents an alternative exon. The occurrence of a termination signal within this alternative transcript is predicted to culminate in a truncated p53 translational product. The sequences of the 371 bp PCR products of Molt-4, HT-1080, SiHa, CaSki, HeLa and MRC-5 cell lines corresponded with the wild-type p53 cDNA. G-->T transversions at the third base of codon 249 of p53 were detected in Mahlavu and PLC/PRF/5 HCC lines, while a TAC to CAC mutation at codon 234 was observed in an allele of the Raji Burkitt lymphoma line.
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PMID:Alternative splicing of the p53 tumor suppressor gene in the Molt-4 T-lymphoblastic leukemia cell line. 822 26

Activating mutations within the p53 gene cause stabilization and therefore increased steady-state levels of the p53 protein; some, but not all, also result in the generation of an epitope recognized by the antibody pAB240. We have shown here that in 70% of Burkitt lymphoma cell lines, but not in normal EBV transformed B cell lines, p53 protein is readily detectable by Western blot analysis using either an antibody directed against the 240 epitope or an antibody against wild-type p53. Genomic analysis of these BL cell lines demonstrated the presence of mutations within the p53 gene in all cell lines with detectable p53 protein. We have also shown that in the cell lines ST486, Raji, and TE 110, which are heterozygous for a neutral sequence codon polymorphism (Arg/Pro) that causes altered migration of an otherwise normal protein and also contain a heterozygous mutation, only the protein derived from the mutated allele is stabilized. Thus the dominant effect of the mutations present in these cell lines apparently does not result from sequestering of the normal protein by the abnormal protein, and therefore presumably is a consequence of a gain-of-function resulting from the mutation. Although all cell lines with stabilized p53 also contained p53 mutations, three lymphoid tumors (two cell lines and one fresh B-CLL) with a heterozygous mutation at codon 248 did not express elevated levels of p53. In contrast, p53 was readily detectable in Western blot analysis from cell lines KK124, Namalwa, and CA46, which had homo- or hemizygous mutations at codon 248, and from PP1084, a cell line with a codon 273 mutation and a carboxyl-terminal truncation in the other allele. These results suggest that mutations at codon 248, unlike those in cell lines ST486 and TE110, are stabilizing only in the absence of the wild-type p53. Heterozygous mutations at codons 248 have been described in the germline of individuals belonging to cancer-prone families described by Li and Fraumeni (see ref 18), but tumors detected in such individuals are homozygous, i.e., contain only mutated p53. This is consistent with the possibility that such mutations exert a pathogenetic effect only in the absence of the wild-type protein, and are coupled to our findings that stabilization of p53 is a necessary component of the oncogenic pathways relevant to p53. However, whereas some mutations are stabilizing in the presence of the normal p53 protein, others are stabilizing only in the homozygous state.
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PMID:Hemi- or homozygosity: a requirement for some but not other p53 mutant proteins to accumulate and exert a pathogenetic effect. 834 93


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