K. Funaoka et al., ACTIVATION OF THE P21(WAF1 CIP1) PROMOTER BY THE ETS ONCOGENE FAMILY TRANSCRIPTION FACTOR E1AF/, Biochemical and biophysical research communications, 236(1), 1997, pp. 79-82
p21(Waf1/Cip1) is one of the key regulatory proteins in cell cycle, te
rminal differentiation, and apoptosis. Its promoter was shown to be tr
ansactivated by the wild-type p53 protein as well as in a p53-independ
ent manner. In this report, we demonstrate that E1AF, an ets-related t
ranscription factor, activated the human p21(Waf1/Cip1) promoter by in
teracting with the ets-binding sites located close to the two previous
ly identified p53-responsive elements. Northern blot analysis revealed
that p21(Waf1/Cip1) and E1AF were correlatively upregulated in respon
se to cisplatin treatment in SiHa cells. Transient expression assays d
emonstrated that E1AF can activate the p21(Waf1/Cip1) promoter-driven
luciferase reporter gene in SiHa cells. The p21(Waf1/Cip1) promoter ac
tivity was also increased in p53-null Saos2 osteosarcoma cells, but wa
s markedly reduced when the ets-binding sites were deleted. These resu
lts indicate that E1AF positively regulates transcription from the p21
(Waf1/Cip1) promoter in response to genotoxic stresses. (C) 1997 Acade
mic Press.