ID p53-php53c1 STANDARD; ss-mRNA; PRI; 1317 bp. XX DE Human p53 cellular tumor antigen mRNA, complete cds. XX AC X02469 M60950 XX DT 22-OCT-1992 XX OS Human, cDNA to mRNA, clone php53c1 from a cDNA library of SV40 OS transformed fibroblasts. OC Homo sapiens OC Eukaryota; Animalia; Chordata; Vertebrata; Mammalia; Theria; OC Eutheria; Primates; Haplorhini; Catarrhini; Hominidae. XX RN [1] RP 1-1317 RA Zakut-Houri,R., Bienz-Tadmor,B., Givol,D. and Oren,M.; RT "Human p53 cellular tumor antigen: cDNA sequence and expression in RT COS cells"; RL EMBO J. 4, 1251-1255 (1985). RN [2] RP 1-1317 RA Rideout,W.M.III., Coetzee,G.A., Olumi,A.F. and Jones,P.A.; RT "5-methylcytosine as anendogenous mutagen in the human ldl receptor RT and p53 genes"; RL Science 249, 1288-1290 (1990). RN [3] RP 1-1317 RA Werness,B.A., Levine,A.J., and Howley,P.M.; RT "Association of Human papillomavirus types 16 and 18 E6 proteins RT with RT p53"; RL Science 248, 76-79 (1990). RN [4] RP 1-1317 RA Scheffner,M., Werness,B.A., Huibregtse,J.M., Levine,A.J., and RA Howley, P.M.; RT "The E6 oncoprotein encoded by Human papillomavirus type 16 and 18 RT promotes the degradation of p53"; RL Cell 63, 1129-1136 (1990). RN [5] RP M14694 and M14695 shown in alignment below RA Harris,N., Brill,E., Shohat,O., Prokocimer,M., Wolf,D., Arai,N. RA and Rotter,V.; RT "Molecular basis for heterogeneity of the human p53 protein"; RL Mol. Cell. Biol. 6, 4650-4656 (1986). RN [6] RP K031991 shown in alignment below RA Harlow,E., Williamson,N.M., Ralston,R., Helfman,D.M. and Adams,T.E.; RT "Molecular cloning and in vitro expression of a cDNA clone for human RT cellular tumor antigen p53"; RL Mol. Cell. Biol. 5, 1601-1610 (1985). XX XX Clone php53c1 is the wild-type form of p53, isolated from an SV40 XX transformed fibroblast cell line. It was first thought that p53, XX a cell-cycle regulatory protein, was an oncogene. This has since XX been disproven, for it has been shown that the clones that were first XX isolated and tested were mutants. In fact, the p53 gene is a tumor XX suppressor. The mutated forms are thought to be trans-dominant XX over the wild-type p53. The mutations cause a conformational change XX in the protein which facilitates its binding to the heat shock XX protein hsp70. The two forms of p53 and hsp70 become bound together XX in long-lived unproductive complexes. Since these complexes aggregate XX in the cytoplasm, the nucleus is deprived of p53. With the XX negative regulatory effect of p53 reduced or eliminated, the cell XX is more easily able to proliferate. However, a different mechanism of XX inactivation is employed by the viral oncoproteins: the large XX T-antigen of SV40 and the E1B 55kD protein of adenovirus. Instead of XX the hsp70, mutant p53 complex trapping the wild-type p53 in inactive XX structures it is the viral oncoproteins that sequester the wild type XX p53 and inactivate it. Human papillomavirus uses yet another XX mechanism. The E6 protein of the oncogenic HPV types bind wild-type XX p53 and stimulate its destruction; although at this point there is no XX evidence that E6 proteins of noncogenic HPV types, such as HPV-6 XX or HPV-11, can associate with wild-type p53 in vivo. It is however XX possible that the binding assay used to determine this fact was not XX sensitive enough to detect low affinity binding. The degradation of XX p53 by HPV E6 is ATP dependant and the ubiquitin-dependant protease XX system has been suggested to be involved. Since the large T antigen XX of SV40 also complexes with wild-type p53 and does not target it for XX degradation, there must be an additional signaling mechanism not yet XX elucidated involved in the interaction with the HPV E6 protein. XX XX The p53 wild type php53c1 coding region and four variants are shown in XX the alignment below. The p53 coding regions which are represented by XX the accession numbers M14694 and M14695 have both been isolated from XX the human transformed cell line SV-80. The two forms differ from one XX another by a single base pair substitution and consequently accounts XX for the change in electrophoretic mobility of the two proteins. The XX author [5] believes that this heterogeneity is due to gene polymorphism. XX The coding region represented by accession number K03199 has been XX isolated from the human vulva carcinoma cell line A431. Accession XX number X54156 corresponds to a genomic p53 coding region. It XX illustrates the the p53 gene organization of 11 exons, and numerous XX ALU flanking regions. There is no information on the cell type that XX was used in this preparation. XX FT KEY Location/Qualifiers FT CDS 136..1317 FT /note="p53 phosphoprotein" FT /gene="TP53" FT /map="17p13.1" FT /codon_start=1 FT repeat_region 354..398 FT /rpt_type=direct FT /rpt_unit=354..368,384..398 FT /note="putative" FT source 1..1317 FT /organism="Homo sapiens" FT /sequenced_mol="cDNA to mRNA" XX SQ SEQUENCE 1317 bp; 295 a; 408 c; 352 g; 262 t; gtctagagcc accgtccagg gagcaggtag ctgctgggct ccggggacac tttgcgttcg 60 ggctgggagc gtgctttcca cgacggtgac acgcttccct ggattggcag ccagactgcc 120 ttccgggtca ctgccatgga ggagccgcag tcagatccta gcgtcgagcc ccctctgagt 180 caggaaacat tttcagacct atggaaacta cttcctgaaa acaacgttct gtcccccttg 240 ccgtcccaag caatggatga tttgatgctg tccccggacg atattgaaca atggttcact 300 gaagacccag gtccagatga agctcccaga atgccagagg ctgctccccc cgtggcccct 360 gcaccagcag ctcctacacc ggcggcccct gcaccagccc cctcctggcc cctgtcatct 420 tctgtccctt cccagaaaac ctaccagggc agctacggtt tccgtctggg cttcttgcat 480 tctgggacag ccaagtctgt gacttgcacg tactcccctg ccctcaacaa gatgttttgc 540 caactggcca agacctgccc tgtgcagctg tgggttgatt ccacaccccc gcccggcacc 600 cgcgtccgcg ccatggccat ctacaagcag tcacagcaca tgacggaggt tgtgaggcgc 660 tgcccccacc atgagcgctg ctcagatagc gatggtctgg cccctcctca gcatcttatc 720 cgagtggaag gaaatttgcg tgtggagtat ttggatgaca gaaacacttt tcgacatagt 780 gtggtggtgc cctatgagcc gcctgaggtt ggctctgact gtaccaccat ccactacaac 840 tacatgtgta acagttcctg catgggcggc atgaaccgga ggcccatcct caccatcatc 900 acactggaag actccagtgg taatctactg ggacggaaca gctttgaggt gcgtgtttgt 960 gcctgtcctg ggagagaccg gcgcacagag gaagagaatc tccgcaagaa aggggagcct 1020 caccacgagc tgcccccagg gagcactaag cgagcactgc ccaacaacac cagctcctct 1080 ccccagccaa agaagaaacc actggatgga gaatatttca cccttcagat ccgtgggcgt 1140 gagcgcttcg agatgttccg agagctgaat gaggccttgg aactcaagga tgcccaggct 1200 gggaaggagc caggggggag cagggctcac tccagccacc tgaagtccaa aaagggtcag 1260 tctacctccc gccataaaaa actcatgttc aagacagaag ggcctgactc agactga 1317 //