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Ultraviolet B Light Induces G₁ 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} Protein¹

Roy M. and Phyllis Gough Huffington Center on Aging and Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030 [E. E. M.]; Departments of Dermatology [S. I., Z. A. A.] and Cell Biology, Neurobiology, and Anatomy [F. Y.], University of Cincinnati, Cincinnati, Ohio 45267-0592; and Department of Dermatology, Ajou University School of Medicine, Suwon 442-749, Korea [S. I.]

UVB irradiation inhibits melanocyte proliferation by causing arrest in G₁ (D. Barker, K. Dixon, E. E. Medrano, D. Smalara, S. Im, D. Mitchell, G. Babcock, and Z. A. Abdel-Malek. Cancer Res., 55: 4041–4046, 1995). To determine how, after UVB irradiation, signal transduction pathways, DNA damage, and cell cycle arrest interact in the human melanocyte, we analyzed here the possible activation of tyrosine kinases, the serine-threonine kinases Raf-1 and ERK2, the status of the transcription factor c-fos, and the activation of cell cycle checkpoints induced by expression of p53 protein. We found that in contrast to the UVC response, exposure to UVB irradiation did not stimulate the above kinases. UVB light induced a prolonged c-fos expression, suggesting a mechanism of induction different from the transient expression elicited by growth factors. The tumor suppressor p53 and the p53-inducible cyclin-dependent 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 product, was halted in UVB-irradiated cells and correlated with the expression of the protein p21^{Waf-1/SDI-1/Cip-1}. Our data define for the first time how UVB irradiation affects the expression of crucial regulatory events needed for cell cycle progression in the human melanocyte.

¹ Supported in part by National Institute on Aging Grant AG 00594-02 (E. E. M.), National Institute of Environmental Health Sciences Grants 1 R01 ES06882-01A1 and 5 P30 ES06096-02 (Z. A. M.), a grant from the Ohio Cancer Research Associates (Z. A. M.), and by the Shiseido Company (Z. A. M.).

² To whom requests for reprints should be addressed, at Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Room M320, Houston, TX 77030.

Received 3/15/95. Accepted 7/19/95.

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