Protein kinase C-delta phosphorylates Ebp1 and prevents its proteolytic degradation, enhancing cell survival.
ErbB3-binding protein (Ebp1) promotes cell survival by preventing apoptotic DNA fragmentation through a complex with active nuclear Akt. Ebp1 phosphorylation by protein kinase C (PKC)-delta mediates its binding to nuclear Akt. In this study, we show that Ebp1 itself acts as a substrate of active caspase 3 during the programmed cell death. PKC-delta phosphorylation on Ebp1 protects it from apoptotic degradation initiated in cell-free apoptotic solution. Moreover, Ebp1 is evidently cleaved in PKC-delta-deficient cells but not in wild-type cells. Ebp1 translated from first ATG is resistant to apoptotic cleavage; by contrast, Ebp1 from second and third ATG demonstrates robust degradation, and PKC phosphorylation on S360 suppresses its cleavage by active caspase 3. Ebp1 can be digested at both D53 and D196 sites, but cleavage at D196 appears to be a prerequisite for its further degradation at D53 site. Compared with wild-type Ebp1, D196A mutant markedly protects cells from apoptosis. Thus, PKC-delta antagonizes apoptosis through phosphorylating Ebp1 and protects it from apoptotic degradation.
Liu
Zhixue
Z
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Liu
Xia
X
Nakayama
Keiichi I
KI
Nakayama
Keiko
K
Ye
Keqiang
K
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000378:metabolism*; D051381:Rats
D048868:Adaptor Proteins, Signal Transducing; C511885:PA2G4 protein, rat; D051745:Protein Kinase C-delta; D053148:Caspase 3