CK1α ablation in keratinocytes induces p53-dependent, sunburn-protective skin hyperpigmentation

Abstract

Significance UV tanning is a common social behavior, which increases melanin production and pigmentation of the skin. UV irradiation is a standard treatment of depigmenting diseases such as vitiligo. However, recurrent UV irradiation is genotoxic and facilitates skin aging and cancer. Here, we identified a method of inducing hyperpigmentation by inhibition of casein kinase 1α (CK1α). UV tanning is induced through activation of p53, via the Pomc/α-MSH/Mc1r/Mitf pathway, but both Pomc and Mc1r function can be compromised by aging or allelic polymorphism. In contrast, inhibition of CK1α activates a different pathway, p53/KitL/Kit, and raises protective eumelanin without the procarcinogenic pheomelanin. Inhibition of CK1α is therefore expected to be an effective strategy for skin protection from sunlight and for treating depigmenting diseases.