ACTIVATION OF THE P21(WAF1 CIP1) PROMOTER BY THE ETS ONCOGENE FAMILY TRANSCRIPTION FACTOR E1AF/

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.