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Oncogene. 2000 Jul 6;19(29):3225-34.

Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16(INK4a) and Cdk2/cyclin E complex activation.

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Basic Technology Research Laboratory, Daiichi Pharamceutical Co. Ltd., Tokyo R&D Center, Japan.


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.

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