Attenuation of UV-induced skin cancer by inhibition of Wip1 activity

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UV-radiation induced DNA damage strongly promotes skin cancer. A major defense against such threat is the suntan response by production of melanin, which is synthesized in skin melanocytes and is then transported into adjacent keratinocytes. There, melanin serves to absorb the UV radiation, as well as neutralize free radicals generated by UV radiation. The p53 tumor suppressor plays a central role in this response. The wild-type p53-induced phosphatase 1 (Wip1) is a regulatory protein for p53 function via a complex negative-feedback regulation mechanism. However, the effect of Wip1 gene on the suntanning process remains unclear. To this aim, we examined the pigmentation process in Wip1 null mice. Compared to wild type mice, Wip1-null mice have much higher expression of melanin protein in the tail and ear without UV stimulation. However, this effect was not observed in the skin of same mouse due to the lack of active epidermal melanocytes. This effect is believed be regulated through activation of p53. This may indicate that loss of Wip1 signaling can result in increased melanocyte biogenesis and hence could enhance the defense against UV radiation-induced skin tumorigenesis. Thus, Wip1 is a potential target to attenuate UV-induced damage via increased melanogenesis.