A PROLIFERATIVE P53-RESPONSIVE ELEMENT MEDIATES TUMOR-NECROSIS-FACTOR-ALPHA INDUCTION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LONG TERMINAL REPEAT

Citation
A. Gualberto et al., A PROLIFERATIVE P53-RESPONSIVE ELEMENT MEDIATES TUMOR-NECROSIS-FACTOR-ALPHA INDUCTION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LONG TERMINAL REPEAT, Molecular and cellular biology, 15(6), 1995, pp. 3450-3459
Citations number
73
Categorie Soggetti
Biology
ISSN journal
02707306
Volume
15
Issue
6
Year of publication
1995
Pages
3450 - 3459
Database
ISI
SICI code
0270-7306(1995)15:6<3450:APPEMT>2.0.ZU;2-9
Abstract
Transforming mutants of the p53 tumor suppressor gene can positively r egulate transcription from several promoters that do not contain known p53 binding sites. Here, we report the identification of a novel p53 binding site in the human immunodeficiency virus long terminal repeat that specifically mediates mutant p53 transactivation, This DNA elemen t was bound by endogenous Jurkat p53 when these cells were stimulated by tumor necrosis factor. Mutation of this sequence inhibited p53 tran sactivation and tumor necrosis factor inducibility of the human immuno deficiency virus type 1 long terminal repeat. In addition, this DNA el ement was found to be sufficient to confer mutant p53 responsiveness o n a heterologous minimal promoter. It has been hypothesized that trans forming mutants of p53 represent a proliferative conformational stage that can he adopted by the native protein under stimulation by growth factors, The data presented suggest that proliferative and antiprolife rative p53 conformations recognize different DNA binding sites in orde r to mediate distinct biological functions. Thus, transforming mutants of p53 that fold into the proliferative conformation would favor prol iferative over antiproliferative functions.