Interaction of HCV core protein with 14-3-3epsilon protein releases Bax to activate apoptosis.
Through protein-protein binding assays, we found that HCV core protein interacted with 14-3-3epsilon protein. Interestingly, the expression of HCV core protein induced apoptosis in 293T cells. The apoptosis induced by core expression is accompanied by translocation of Bax from cytosol to mitochondria, disruption of mitochondrial membrane potential, cytochrome c release, and activation of caspase-9 and caspase-3. Furthermore, over-expression of 14-3-3epsilon inhibited the core-induced apoptosis and Bax translocation to mitochondria. These results indicate that HCV core protein induces the Bax-mediated apoptosis by interacting with 14-3-3epsilon protein in 293T cells. As a mechanism of apoptosis induction by HCV core, we propose that the interaction of HCV core with 14-3-3epsilon causes the dissociation of Bax from the Bax/14-3-3epsilon complex in cytosol, and the free Bax protein provokes activation of the mitochondrial apoptotic pathway.
Lee
Sang Kyu
SK
Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Republic of Korea.
Park
Sun Ock
SO
Joe
Cheol O
CO
Kim
Young Sang
YS
D048948:14-3-3 Proteins / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D014758:Viral Core Proteins / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D048948:14-3-3 Proteins; C494826:BAX protein, human; D014758:Viral Core Proteins; C482983:YWHAE protein, human; D051028:bcl-2-Associated X Protein