LOCUS p53-php53c1 1317 bp ss-mRNA PRI 22-OCT-1992 DEFINITION Human p53 cellular tumor antigen mRNA, complete cds. ACCESSION X02469 M60950 KEYWORDS antigen; tumor antigen. SOURCE Human, cDNA to mRNA, clone php53c1 from a cDNA library of SV40 transformed fibroblasts. ORGANISM Homo sapiens Eukaryota; Animalia; Chordata; Vertebrata; Mammalia; Theria; Eutheria; Primates; Haplorhini; Catarrhini; Hominidae. REFERENCE 1 (bases 1 to 1317) AUTHORS Zakut-Houri,R., Bienz-Tadmor,B., Givol,D. and Oren,M. TITLE Human p53 cellular tumor antigen: cDNA sequence and expression in COS cells JOURNAL EMBO J. 4, 1251-1255 (1985) STANDARD full staff_review REFERENCE 2 (bases 1 to 1317) AUTHORS Rideout,W.M.III., Coetzee,G.A., Olumi,A.F. and Jones,P.A. TITLE 5-methylcytosine as anendogenous mutagen in the human ldl receptor and p53 genes JOURNAL Science 249, 1288-1290 (1990) STANDARD full staff_review REFERENCE 3 (bases 1 to 1317) AUTHORS Werness,B.A., Levine,A.J., and Howley,P.M. TITLE Association of Human papillomavirus types 16 and 18 E6 proteins with p53 JOURNAL Science 248, 76-79 (1990) STANDARD full staff_review REFERENCE 4 (bases 1 to 1317) AUTHORS Scheffner,M., Werness,B.A., Huibregtse,J.M., Levine,A.J., and Howley, P.M. TITLE The E6 oncoprotein encoded by Human papillomavirus type 16 and 18 promotes the degradation of p53 JOURNAL Cell 63, 1129-1136 (1990) STANDARD full staff_review REFERENCE 5 (M14694 and M14695 shown in alignment below) AUTHORS Harris,N., Brill,E., Shohat,O., Prokocimer,M., Wolf,D., Arai,N. and Rotter,V. TITLE Molecular basis for heterogeneity of the human p53 protein JOURNAL Mol. Cell. Biol. 6, 4650-4656 (1986) STANDARD full staff_review REFERENCE 6 (K031991 shown in alignment below) AUTHORS Harlow,E., Williamson,N.M., Ralston,R., Helfman,D.M. and Adams,T.E. TITLE Molecular cloning and in vitro expression of a cDNA clone for human cellular tumor antigen p53 JOURNAL Mol. Cell. Biol. 5, 1601-1610 (1985) STANDARD full staff_review COMMENT Clone php53c1 is the wild-type form of p53, isolated from an SV40 transformed fibroblast cell line. It was first thought that p53, a cell-cycle regulatory protein, was an oncogene. This has since been disproven, for it has been shown that the clones that were first isolated and tested were mutants. In fact, the p53 gene is a tumor suppressor. The mutated forms are thought to be trans-dominant over the wild-type p53. The mutations cause a conformational change in the protein which facilitates its binding to the heat shock protein hsp70. The two forms of p53 and hsp70 become bound together in long-lived unproductive complexes. Since these complexes aggregate in the cytoplasm, the nucleus is deprived of p53. With the negative regulatory effect of p53 reduced or eliminated, the cell is more easily able to proliferate. However, a different mechanism of inactivation is employed by the viral oncoproteins: the large T-antigen of SV40 and the E1B 55kD protein of adenovirus. Instead of the hsp70, mutant p53 complex trapping the wild-type p53 in inactive structures it is the viral oncoproteins that sequester the wild type p53 and inactivate it. Human papillomavirus uses yet another mechanism. The E6 protein of the oncogenic HPV types bind wild-type p53 and stimulate its destruction; although at this point there is no evidence that E6 proteins of noncogenic HPV types, such as HPV-6 or HPV-11, can associate with wild-type p53 in vivo. It is however possible that the binding assay used to determine this fact was not sensitive enough to detect low affinity binding. The degradation of p53 by HPV E6 is ATP dependant and the ubiquitin-dependant protease system has been suggested to be involved. Since the large T antigen of SV40 also complexes with wild-type p53 and does not target it for degradation, there must be an additional signaling mechanism not yet elucidated involved in the interaction with the HPV E6 protein. The p53 wild type php53c1 coding region and four variants are shown in the alignment below. The p53 coding regions which are represented by the accession numbers M14694 and M14695 have both been isolated from the human transformed cell line SV-80. The two forms differ from one another by a single base pair substitution and consequently accounts for the change in electrophoretic mobility of the two proteins. The author [5] believes that this heterogeneity is due to gene polymorphism. The coding region represented by accession number K03199 has been isolated from the human vulva carcinoma cell line A431. Accession number X54156 corresponds to a genomic p53 coding region. It illustrates the the p53 gene organization of 11 exons, and numerous ALU flanking regions. There is no information on the cell type that was used in this preparation. FEATURES Location/Qualifiers CDS 136..1317 /note="p53 phosphoprotein" /gene="TP53" /map="17p13.1" /codon_start=1 /translation="MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLM LSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKT YQGSYGFRLGFLHSGTAKSVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAM AIYKQSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVV PYEPPEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCA CPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRG RERFEMFRELNEALELKDAQAGKEPGGSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDS D" repeat_region 354..398 /rpt_type=direct /rpt_unit=354..368,384..398 /note="putative" source 1..1317 /organism="Homo sapiens" /sequenced_mol="cDNA to mRNA" BASE COUNT 295 a 408 c 352 g 262 t ORIGIN 2 bp upstream of XbaI site; chromosome 17p13. 1 gtctagagcc accgtccagg gagcaggtag ctgctgggct ccggggacac tttgcgttcg 61 ggctgggagc gtgctttcca cgacggtgac acgcttccct ggattggcag ccagactgcc 121 ttccgggtca ctgccatgga ggagccgcag tcagatccta gcgtcgagcc ccctctgagt 181 caggaaacat tttcagacct atggaaacta cttcctgaaa acaacgttct gtcccccttg 241 ccgtcccaag caatggatga tttgatgctg tccccggacg atattgaaca atggttcact 301 gaagacccag gtccagatga agctcccaga atgccagagg ctgctccccc cgtggcccct 361 gcaccagcag ctcctacacc ggcggcccct gcaccagccc cctcctggcc cctgtcatct 421 tctgtccctt cccagaaaac ctaccagggc agctacggtt tccgtctggg cttcttgcat 481 tctgggacag ccaagtctgt gacttgcacg tactcccctg ccctcaacaa gatgttttgc 541 caactggcca agacctgccc tgtgcagctg tgggttgatt ccacaccccc gcccggcacc 601 cgcgtccgcg ccatggccat ctacaagcag tcacagcaca tgacggaggt tgtgaggcgc 661 tgcccccacc atgagcgctg ctcagatagc gatggtctgg cccctcctca gcatcttatc 721 cgagtggaag gaaatttgcg tgtggagtat ttggatgaca gaaacacttt tcgacatagt 781 gtggtggtgc cctatgagcc gcctgaggtt ggctctgact gtaccaccat ccactacaac 841 tacatgtgta acagttcctg catgggcggc atgaaccgga ggcccatcct caccatcatc 901 acactggaag actccagtgg taatctactg ggacggaaca gctttgaggt gcgtgtttgt 961 gcctgtcctg ggagagaccg gcgcacagag gaagagaatc tccgcaagaa aggggagcct 1021 caccacgagc tgcccccagg gagcactaag cgagcactgc ccaacaacac cagctcctct 1081 ccccagccaa agaagaaacc actggatgga gaatatttca cccttcagat ccgtgggcgt 1141 gagcgcttcg agatgttccg agagctgaat gaggccttgg aactcaagga tgcccaggct 1201 gggaaggagc caggggggag cagggctcac tccagccacc tgaagtccaa aaagggtcag 1261 tctacctccc gccataaaaa actcatgttc aagacagaag ggcctgactc agactga