Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death.
Caspase 3 is an essential death factor for the Fas-mediated cell death, and its inactivation in cells is initiated by an interaction with p21 on mitochondria or with IAP family member ILP. Survivin is also a member of IAP family and is specifically expressed during embryogenesis and in tumor cells and suppresses cell death signaling. In our current study, we demonstrated that Survivin translocation into the nucleus is dependent on Fas stimulation and cell proliferation. Survivin also interacts with the cell cycle regulator Cdk4, leading to Cdk2/Cyclin E activation and Rb phosphorylation. As a result of Survivin/Cdk4 complex formation, p21 is released from its complex with Cdk4 and interacts with mitochondrial procaspase 3 to suppress Fas-mediated cell death. Here, we propose that Survivin supports procaspase 3/p21 complex formation as a result of interaction with Cdk4 resulting in suppression of cell death signaling.
Suzuki
A
A
Project for the Cell Death Research, Basic Technology Research Laboratory, Daiichi Pharmaceutical Co. Ltd., Tokyo R&D Center, Kitakasai 1-16-13, Edogawa-ku, Tokyo 134-8630, Japan.
Ito
T
T
Kawano
H
H
Hayashida
M
M
Hayasaki
Y
Y
Tsutomi
Y
Y
Akahane
K
K
Nakano
T
T
Miura
M
M
Shiraki
K
K
D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D002470:Cell Survival; D051358:Cyclin-Dependent Kinase 4; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D008954:Models, Biological; D009363:Neoplasm Proteins; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D000077022:Survivin; D019014:fas Receptor / Q000378:metabolism*
C107489:BIRC5 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004792:Enzyme Precursors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D000077022:Survivin; D019014:fas Receptor; C030193:immunosuppressive acidic protein; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases