Protein kinase C-epsilon protects MCF-7 cells from TNF-mediated cell death by inhibiting Bax translocation.
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.
Lu
Dongmei
D
Department of Molecular Biology & Immunology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
Sivaprasad
Usha
U
Huang
Jie
J
Shankar
Eswar
E
Morrow
Shavonda
S
Basu
Alakananda
A
D000818:Animals; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D019281:Dimerization; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D051744:Protein Kinase C-epsilon