The involvement of prohibition in Akt and Raf co‐regulated apoptosis of HaCaT keratinocytes upon UVB irradiation

Abstract

Prohibitin (PHB) is involved in regulation of many cell functions, such as cell‐cycle control, cell proliferation, senescence, apoptosis, and tumor suppression. However, the roles of PHB in regulation of UVB‐induced apoptosis of keratinocytes are largely unknown. In this study, we evaluated the role of PHB in regulation of Akt and Raf activity in UVB‐irradiated HaCaT cells. Our data showed that PHB was localized to the membrane from the cytosol upon UVB irradiation. A co‐immunoprecipitation analysis indicated that UVB altered the interaction among PHB, Raf, and Akt. Using siRNA‐mediated knockdown as well as stable shRNA‐mediated knockdown, we demonstrated that upon UVB irradiation, the cells with reduced expression of PHB showed an increase in apoptosis, as well as an increased phosphorylation of Akt and a decreased phosphorylation of ERK. In addition, our data showed that the effect of L‐NAC on UVB‐induced apoptosis is independent of PHB knockdown, which suggests that the PHB‐knockdown‐mediated cell apoptosis is independent of UVB‐induced oxidative stress. Based on these results, we propose that PHB regulates UVB‐induced apoptosis of keratinocytes via Akt and Raf, not the oxidative‐stress signaling pathway.This work is funded by NIH RO1 CA086928 (to S. W.)