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
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.