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Titolo:
Direct transactivation of c-Ha-Ras gene by p53: evidence for its involvement in p53 transactivation activity and p53-mediated apoptosis
Autore:
Deguin-Chambon, V; Vacher, M; Jullien, M; May, E; Bourdon, JC;
Indirizzi:
CEA, DSV, UMR217 CNRS, Lab Cancerogenese Mol, F-92265 Fontenay Aux Roses, France CEA Fontenay Aux Roses France F-92265 F-92265 Fontenay Aux Roses, France Univ Dundee, Dept Biochem, CRC, Cell Transformat Res Grp, Dundee DD1 4HN, Scotland Univ Dundee Dundee Scotland DD1 4HN at Res Grp, Dundee DD1 4HN, Scotland
Titolo Testata:
ONCOGENE
fascicolo: 51, volume: 19, anno: 2000,
pagine: 5831 - 5841
SICI:
0950-9232(20001130)19:51<5831:DTOCGB>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; CELL-CYCLE MACHINERY; TUMOR-SUPPRESSOR P53; WILD-TYPE P53; BINDING-SITE; NEUROBLASTOMA-CELLS; PHORBOL ESTER; FIRST INTRON; T-ANTIGEN; IN-VITRO;
Keywords:
p53 RE; c-Ha-Ras; transactivation; Ras.GTP; p53-stability;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: May, E CEA, DSV, UMR217 CNRS, Lab Cancerogenese Mol, BP6, F-92265 FontenayAux Roses, France CEA BP6 Fontenay Aux Roses France F-92265 ntenay Aux Roses, France
Citazione:
V. Deguin-Chambon et al., "Direct transactivation of c-Ha-Ras gene by p53: evidence for its involvement in p53 transactivation activity and p53-mediated apoptosis", ONCOGENE, 19(51), 2000, pp. 5831-5841

Abstract

p53 protein is a sequence-specific transcriptional activator which inducesthe expression of a number of cellular genes involved in different metabolic pathways, We report that the computer-selected sequence in human and mouse C-Ha-Ras gene confers to a reporter gene the ability to be directly transactivated by wild-type p53 either ovrespressed or activated in response toa cellular stress. By analysing human transformed cell lines, we showed, at both mRNA and protein level, that the endogenous C-Ha-Ras gene expressionis positively regulated by wt p53 protein, The stimulation of c-Ha-Ras gene expression in Saos-2Ts cells by a temperature shift down to the permissive temperature for the p53-wt conformation is associated with a significant increase in the activated form of p21(e-11a-Ras) protein. Furthermore, in human transformed cell lines, the transient expression of a dominant interfering mutant of c-Ha-Ras greatly reduced the ability of p53 to induce apoptosis and inhibited the p53-dependent transactivation. This is due, at least in part, to a decrease in the protein (but not mRNA) level of the transiently expressed p53, indicating that inactivation of p21(e-11a-Ras) signallingpathways led to a specific degradation of p53 protein, We therefore suggest that, by inducing c-Ha-Ras, p53 activates a positive feedback loop that counteracts the negative feedback loop mediated by Mdm2.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 19:30:34