A single gene and a pseudogene for the cellular tumour antigen p53

Zakut-Houri, R; Oren, Moshe; Bienz, B; Lavie, Vered; Hazum, Shula; Givol, David

doi:10.1038/306594a0

Cited by 200 publications

(132 citation statements)

References 27 publications

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“…It is possible that the part of the LTR contained in pKCR 42 but not in pKCR 42RP may be inhibitory to transcription or translation. Although the predicted molecular weight, 21000, appears different from that observed, 28000, this may be due to the unusually high content of proline (18~) causing a slower mobility of the protein in SDScontaining gels (Zakut-Houri et al, 1983). Similar behaviour is observed for gag p19 whose molecular weight is estimated as 14000 and contains 19~o proline.…”

Section: ~supporting

confidence: 54%

Structural Analysis of p28 Adult T-Cell Leukaemia-associated Antigen

Iino

Takeuchi

Nam

et al. 1986

Journal of General Virology

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SUMMARYThe 28 000 mol. wt. polypeptide (p28) of adult T-cell leukaemia-associated antigen encoded by the 24S defective human T-cell leukaemia virus (HTLV-I) is associated with protein kinase activity. We have determined the nucleotide sequence of this defective HTLV-I provirus and found that it contains a portion of the gag gene (p19 and part of p24), the pX region, and two long terminal repeats, one at each end. The predicted p28 gag-pX fused protein consists of 190 amino acids and its mol. wt. was calculated as 21055. The results of peptide mapping analysis showing that p28 contains p19 supported the nucleotide sequence data. That p28 was encoded by this defective provirus was also demonstrated by transient expression of p28 polypeptide in COS 7 cells transfected with a recombinant plasmid containing a simian virus 40 early promoter and the p28-coding region of the 24S HTLV-I.

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Section: ~supporting

confidence: 54%

Structural Analysis of p28 Adult T-Cell Leukaemia-associated Antigen

Iino

Takeuchi

Nam

et al. 1986

Journal of General Virology

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“…Analysis of genomic DNA by using p53 cDNA probes showed the existence of two noncontiguous p53 genes, one which is probably a pseudogene contained within a 3.3-kb EcoRI fragment and a second within a 16.0-kb EcoRI fragment (25,46). We (47), and the sub- (26,46). The first exon, found at the extreme 5' proximal end, was most noticeably separated from the second exon and the major exon clusters by an intron of 6 kb (47).…”

Section: Resultsmentioning

confidence: 99%

“…7, probe p8RH.3). Subclone p8RH.4, corresponding to the last exon and the 3' noncoding region (47), only hybridized to the mature p53 2.0-kb species expressed in the 230-23-8 p53 producer cells. Hybridization with the Kpn-Kpn Moloney LTR-specific probe or fragments of the pL2.H L12 p53 gene (Hind-Pst representing the LTR; Pst-Hind representing the gag-pol sequences) (see Fig.…”

Section: Clone P8r2h)mentioning

confidence: 99%

Inactivation of p53 gene expression by an insertion of Moloney murine leukemia virus-like DNA sequences.

Wolf¹,

Rotter²

1984

Mol. Cell. Biol.

112

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Analysis of Abelson murine leukemia virus-transformed L12 cells which lack the p53 cellular encoded tumor antigen revealed alterations in the p53-specific genomic DNA sequences. The active p53 gene, usually contained in a 16-kilobase EcoRI DNA fragment of p53 producer cells, went through major alterations leading to the appearance of a substantially larger 28.0-kilobase p53-specific EcoRI fragment. Detailed restriction enzyme analysis, with genomic probes spanning throughout the whole active p53 gene, indicated that the L12 p53 altered gene contains all the exons and principal introns of the normal p53 16.0-kilobase gene. However, its structure was interrupted by the integration of a novel DNA segment into the noncoding intervening sequences of the first p53 intron. Analysis of the inserted sequences revealed close homology to Moloney murine leukemia virus. This Moloney leukemia murine virus-like particle resides in a 5' to 3' transcriptional orientation, similar to the p53 gene, permitting the transcription of aberrant fused mRNA molecules detected in these cells.p53 is a cellular encoded protein that is overproduced in cancer cells. Accentuated concentrations of this protein were detected in a variety of cell lines and primary tumors of several species (6,7,9,16,17,30,33,39), suggesting that p53 may play a role in neoplastic transformation. In tumor cells this protein was found in its phosphorylated form (13,20,30,32), and in several instances it was found in a stable complex with viral tumor antigens (16,17,19,37). A limited occurrence of p53 was also observed in nontransformed cells, such as normal thymocytes (34), primary embryonic fibroblasts (24), and NIH-3T3 fibroblasts (27). It was suggested that p53 may display a function in the normal cell cycle (21,23,24).The function that p53 fulfills in transformed and nontransformed cells can be understood by comparing cells that express the protein and variant cells that do not express it. We have at our disposal a unique Abelson murine leukemia virus (Ab-MuLV)-transformed cell line, L12, which lacks detectable amounts of the p53 protein. Injection of these cells into syngeneic mice induced the development of tumors which were subsequently rejected, whereas other AbMuLV-transformed cells that were overproducing p53 developed into lethal tumors (31,45). This observation suggests a correlation between expression of p53 in tumor cells and their capacity to exhibit a fully transformed phenotype, evaluated as development of lethal tumors in syngeneic mice.In our previous studies employing specific cDNA probes (25, 26), we found that the inability of L12 cells to produce p53 is due to the absence of detectable mature p53-specific mRNA (46). Instead, these cells contain two major p53-specific mRNA species of a substantially larger size than the p53-specific mRNA in the p53 producing cells (46 RNA and DNA blot analysis. RNA was prepared according to the method of Auffray and Rougeon (1)

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“…Loss of heterozygosity (LOH) was frequently observed on multiple chromosome loci in SCLC (Hosoe et al, 1994;Merlo et al, 1994a;Mori et al, 1990;Miller et al, 1992). Several candidate tumor suppressor genes located on these chromosome loci were identi®ed, such as the FHIT gene (Ohta et al, 1996a), the RB gene (Mori et al, 1990), and the p53 gene (Zakut-Houri et al, 1983;Matlashewski et al, 1984). However, other potential tumor suppressor genes that may play roles in SCLC have not yet been found.…”

Section: Introductionmentioning

confidence: 99%

Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines

Kim

et al. 1998

Oncogene

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Loss of heterozygosity (LOH) at chromosome 10q23-q25 is frequent in small cell lung cancer (SCLC), indicating the presence of putative tumor suppressor genes. PTEN/ MMAC1, a newly cloned candidate tumor suppressor gene at 10q23, was mutated in multiple human cancers. We investigated whether mutations of PTEN/MMAC1 play an important role in SCLC tumorigenesis. We examined 16 SCLC cell lines for PTEN/MMAC1 mRNA expression by reverse-transcriptase polymerase chain reaction (RT ± PCR) and potential mutations by sequencing analysis of the PTEN/MMAC1 coding region. No mutation was observed in PTEN/MMAC1 cDNAs in 15 cell lines expressing PTEN/MMAC1. One SCLC cell line, DMS79, did not have detectable PTEN/ MMAC1 expression. Importantly, we identi®ed a novel homologue of PTEN/MMAC1, termed PTH2, localized to chromosome 9p21-q13 and containing only ten amino acid substitutions compared with the PTEN/MMAC1 coding region. However, because the putative initiation codon for PTEN/MMAC1 gene was changed to arginine in PTH2, the translational initiation site of PTH2 is very likely to di er from that of the PTEN/MMAC1. PTH2 was expressed in two normal lung tissues and two normal colon tissues, but in only four of 16 SCLC cell lines. A missense mutation in PTH2 was identi®ed in a SCLC cell line that did not express PTEN/MMAC1 mRNA. Our data suggest that inactivation of PTEN/ MMAC1 is a rare event in SCLC tumorigenesis. However, the PTEN/MMAC1 homologue PTH2 may play a role in SCLC tumorigenesis.

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A single gene and a pseudogene for the cellular tumour antigen p53

Cited by 200 publications

References 27 publications

Structural Analysis of p28 Adult T-Cell Leukaemia-associated Antigen

Structural Analysis of p28 Adult T-Cell Leukaemia-associated Antigen

Inactivation of p53 gene expression by an insertion of Moloney murine leukemia virus-like DNA sequences.

Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines

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