Protein kinase C-ε protects MCF-7 cells from TNF-mediated cell death by inhibiting Bax translocation

We have previously shown that protein kinase C epsilon (PKC epsilon) acts as an antiapoptotic protein and protects breast cancer MCF-7 cells from tumor necrosis factor-a (TNF)-mediated apoptosis. In the present study, we have investigated the mechanism by which PKC epsilon- inhibits TNF-induced cell death. Overexpression of wild-type PKC epsilon (WT-PKC epsilon) in MCF-7 cells decreased TNF-induced mitochondrial depolarization. Depletion of Bax by small interfering RNA (siRNA) attenuated TNF-induced cell death. Overexpression of PKCe in MCF-7 cells decreased dimerization of Bax and its translocation to the mitochondria. Knockdown of PKCe using siRNA induced Bax dimerization and mitochondrial translocation. PKC epsilon was coimmunoprecipitated with Bax in MCF-7 cells. These results suggest that PKCe mediates its antiapoptotic effect partly by preventing activation and translocation of Bax to the mitochondria.