ULTRAVIOLET-B LIGHT INDUCES G(1) ARREST IN HUMAN MELANOCYTES BY PROLONGED INHIBITION OF RETINOBLASTOMA PROTEIN-PHOSPHORYLATION ASSOCIATED WITH LONG-TERM EXPRESSION OF THE P21(WAF-1 SDI-1/CIP-1) PROTEIN/

UVB irradiation inhibits melanocyte proliferation by causing arrest in G(1) (D. Barker, K. Dixon, E. E. Medrano, D. Smalara, S. Im, D. Mitch ell, G. Babcock, and Z. A. Abdel-Malek. Cancer Res., 55: 4041-4046, 19 95). To determine how, after UVB irradiation, signal transduction path ways, DNA damage, and cell cycle arrest interact in the human melanocy te, we analyzed here the possible activation of tyrosine kinases, the serine-threonine kinases Raf-1 and ERK2, the status of the transcripti on factor c-fos, and the activation of cell cycle checkpoints induced by expression of p53 protein. We found that in contrast to the UVC res ponse, exposure to UVB irradiation did not stimulate the above kinases . UVB light induced a prolonged c-fos expression, suggesting a mechani sm of induction different from the transient expression elicited by gr owth factors. The tumor suppressor p53 and the p53-inducible cyclin-de pendent kinase inhibitor protein p21(Waf-1/SDI-1/Cip-1) were expressed at high levels for at least 2 days after UV-irradiation. In parallel, phosphorylation of Rb, the retinoblastoma tumor suppressor gene produ ct, was halted in UVB-irradiated cells and correlated with the express ion of the protein p21(Waf-1/SDI-1/Cip-1). Our data define for the fir st time how UVB irradiation affects the expression of crucial regulato ry events needed for cell cycle progression in the human melanocyte.