Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16(INK4a) and Cdk2/cyclin E complex activation.
Survivin is observed uniquely in tumor cells and developmental cells, which undergo either inappropriate or programmed cell growth. In the current study, we investigated the influence of Survivin on cell cycle. Overexpression of Survivin resulted in accelerated S phase shift, resistance to G1 arrest, and activated Cdk2/Cyclin E complex leading Rb phosphorylation. In addition, nuclear translocation of Survivin followed by an interaction with Cdk4 was detected. Interestingly, Survivin nuclear translocation coincided with S phase shift, and prevention of nuclear transport suppressed Survivin nuclear translocation and S phase shift. Further, we also observed that Survivin competitively interacted with the Cdk4/p16(INK4a) complex in a cell free system and in vivo. These results suggest that Survivin initiates the cell cycle entry as a result of nuclear translocation followed by an interaction with Cdk4.
Basic Technology Research Laboratory, Daiichi Pharamceutical Co. Ltd., Tokyo R&D Center, Japan.
A
A
Suzuki
M
M
Hayashida
T
T
Ito
H
H
Kawano
T
T
Nakano
M
M
Miura
K
K
Akahane
K
K
Shiraki
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001667:Binding, Competitive; D001692:Biological Transport; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009500:Neutralization Tests; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D000077022:Survivin; D014407:Tumor Cells, Cultured
C107489:BIRC5 protein, human; D002352:Carrier Proteins; D019927:Cyclin E; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D000077022:Survivin; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases