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

• DOI: 10.1007/s10495-007-0111-7
• Publication Date: 2007-07-31T12:21:37Z
• Authors: Dongmei Lu; Usha Sivaprasad; Jie Huang; Eswar Shankar; Shavonda Morrow; Alakananda Basu
• Keywords: 0301 basic medicine; Cell Death; Tumor Necrosis Factor-alpha; Protein Kinase C-epsilon; Mitochondria; Protein Transport; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Female; RNA, Small Interfering; Dimerization; bcl-2-Associated X Protein

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