The loss of the tumor suppressor gene product p16 in melanoma is well docum
ented, although the normal physiological function of p16 in skin melanocyte
s is unknown. Zn this report, we demonstrate that when human skin was irrad
iated with suberythemal doses of UV radiation, levels of p16 were dramatica
lly increased by 16 h postirradiation, peaking at 24 h, and declining by 72
h, p16 was expressed in the nucleus and cytoplasm of melanocytes and kerat
inocytes within the epidermis, and the pattern of p16 expression within the
epidermis was dependent on the penetrative ability of the different UV wav
ebands. The existence of a UV-induced response pathway involving up-regulat
ed p16 expression may provide a mechanism linking the loss of p16 and UV ex
posure with the development of melanoma.