Induction of apoptosis by p110C requires mitochondrial translocation of the proapoptotic BCL-2 family member BAD.
p110C, a 50-kDa isoform of the PITSLRE kinase family, was demonstrated to play an important role in cell apoptosis. However, how p110C exactly promotes apoptosis is unclear. Our previous study showed that p110C interacted with p21-activated kinase 1 (PAK1), an important kinase of the proapoptotic BCL-2 family member BAD, and evidently inhibited its kinase activity. Here, we report that overexpression of p110C leads to decreased phosphorylation of BAD and its subsequent translocation from cytosol to mitochondria, which in turn induces the release of cytochrome c and the onset of apoptosis. Knocking down endogenous BAD expression will inhibit p110C induced apoptosis. Two kinase dead forms of p110C, D149N and K36N, lose the ability to inhibit the kinase activity of PAK1 and fail to induce the translocation of BAD and the BAD and such proapoptotic ability is associated with the kinase activity of p110C.
Chen
Chen
C
State Key Laboratory of Genetic Engineering and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032, PR of China.
Yan
Jun
J
Sun
Qing
Q
Yao
Luyang
L
Jian
Yongzhi
Y
Lu
Jieqiong
J
Gu
Jianxin
J
D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D017354:Point Mutation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D014162:Transfection; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism*
C494819:BAD protein, human; D007527:Isoenzymes; D051025:bcl-Associated Death Protein; D045304:Cytochromes c; C447612:CDK11a protein, human; D018844:Cyclin-Dependent Kinases