Endogenous survivin modulates survival andproliferation in UVB-treated human keratinocytes

Survivin is a bi-functional member of inhibitor ofapoptosis protein family, as it is able to both inhibit apoptosisand to regulate cell cycle. We investigated the role of survivin inhuman keratinocytes under normal conditions and during UVBirradiation. Survivin siRNA decreases proliferation and inducesapoptosis in human keratinocytes, in a mode consistent with themitotic catastrophe. Low doses UVB increase survivin expressionat earlier times, while high doses down-regulate survivin level.Low doses UVB induce cell cycle arrest in G2 ⁄ M, while highdoses UVB cause apoptosis. Moreover, overexpression of survivinprotects keratinocytes from UVB-induced apoptosis, and silencingof survivin renders keratinocytes more susceptible to UVBinducedcell death. Finally, survivin siRNA increases UVB-inducedreduction of cell proliferation. Taken together, these resultsindicate that survivin plays a critical role in epidermalhomeostasis in normal conditions and during UVB exposure, withpossible implication in skin carcinogenesis.