CELL CYCLE-DEPENDENT MODULATION OF PROMOTER ACTIVITIES OF RB AND WAF1CIP1 GENES/

A universal inhibitor of cyclin-dependent kinases, WAF1/Cip1 can depho sphorylate the RB gene product to arrest the cell cycle at the G1 phas e. Here we show that the mRNA level and the promoter activities of the RE and WAF1/Cip1 genes exhibit cell cycle dependent change when cells are released from either serum-starvation or the confluent cell state with serum. RE expression and promoter activity are elevated at middl e to late G1, In contrast, the mRNA and promoter activity of the WAF1/ /Cip1 gene increase at early G1. These results suggest that the RB and WAF1/Cip1 expression and promoter activities depend not only on serum , but also on the cell cycle progression itself, Moreover, we identifi ed the responsive region for serum-released cell cycle progression in the RE promoter and mapped it to the region between -4 and -182 relati ve to the initiating codon of the RE gene. The region in the WAF1/Cip1 promoter responsible for the serum-released cell cycle progression ma pped not to the p53 binding site, but to the 374 base-pair region betw een -1770 and -1396 from the transcription start site.