A P53-INDEPENDENT PATHWAY FOR INDUCTION OF P21(WAF1CIP1) AND CONCOMITANT G(1) ARREST IN UV-IRRADIATED HUMAN SKIN FIBROBLASTS

Largely on the basis of studies using the potent clastogen ionizing ra diation, it has been widely assumed that up-regulation of the cyclin-d ependent kinase inhibitor p21(waf1cip1) in cultured cells exposed to D NA-damaging agents is contingent upon the presence of functional p53 t umor suppressor protein. Nevertheless, we demonstrate here that the mo del mutagen 254-nm UV light induces p21(waf1cip1) protein and concomit ant G(1) arrest in normal human skin fibroblasts, as well as in p53-de ficient fibroblasts derived from cancer-prone Li-Fraumeni syndrome pat ients, However, as expected, following exposure to ionizing radiation, elevated p21(waf1cip1) protein levels and G(1) arrest were observed o nly in normal fibroblasts, These data provide a prominent and clinical ly relevant example in which p21(waf1cip1)-mediated growth arrest occu rs independently of p53 in human cells treated with a model DNA-damagi ng agent.