UV-B A IRRADIATION OF MOUSE KERATINOCYTES RESULTS IN P53-MEDIATED WAF1/CIP1 EXPRESSION/

The tumor suppressor gene p53 is involved in controlling cell cycle ch eckpoint or triggering apoptosis. p53 may accomplish these roles by ac ting as a sequence-specific transcription factor, One of the downstrea m targets of p53 transcription control is the WAF1/CIP1 gene, whose ge ne product p21 interacts with several cyclins and cyclin-dependent kin ases, resulting in inhibition of these kinases. Tn our previous studie s, we have shown that the p53 protein level in mouse keratinocytes was elevated following UV-B/A irradiation. In this paper we further inves tigated the consequences of increased p53 protein level by characteriz ing p53 DNA-binding level and WAF1/CIP1 gene expression in UV-B/A-irra diated mouse keratinocytes. Consistent with the increased level of p53 protein, both p53 DNA-binding level and steady-state level of WAFI/CI P1 mRNA were elevated. We have demonstrated that the induction of WAF1 /CIP1 mRNA was mediated by p53, since no WAF1/CIP1 induction was obser ved in p53-deficient cells upon W-B exposure. These observations sugge st an important role for the tumor suppressor gene p53 in the response of keratinocytes to the biologically relevant W-BIA irradiation and i n suppressing UV-induced skin cancer.