Ultraviolet B (UVB) light is a potential environmental carcinogen, which has been shown to cause various skin cancers. Normally, UV-damaged cells are eliminated by the self-protective apoptosis response. UVB-induced apoptosis can be regulated by modification of major lipid raft components, such as cholesterol and ceramide. Upon UVB irradiation, an alteration of lipid raft composition leads to the recruitment/activation of raft-associated proteins and initiates downstream apoptotic signaling pathways. To identify potential regulators of UVB-induced apoptosis, we used 2D gel electrophoresis to identify the raft proteins that are altered after UVB-irradiation. Our data shows that levels of several raft proteins, including prohibitin (PHB), were changed after UVB-irradiation. PHB plays a critical role in many cell functions, such as cell-cycle control, cell proliferation, senescence, development, apoptosis, and tumor suppression. However, no reports implicate PHB-mediated apoptosis upon UVB irradiation. We now demonstrate that while the total PHB expression does not change, PHB is enriched in lipid rafts after UVB irradiation. Immunoprecipitation analysis shows that UVB alters the binding ability of PHB, Raf, and Akt, and decrease PHB phosphorylation. PHB siRNA knockdown cells exhibited an increased phosphorylation of Akt and ERK, and increased cell apoptosis after UVB irradiation. Based on these results, we propose that PHB regulates UVB-induced apoptosis through lipid raft translocation and alteration of Akt and Raf/ERK signaling pathways.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3012. doi:1538-7445.AM2012-3012