It is possible that UCN-01 inhibits CAK indirectly. One may speculate that CDK inhibitor proteins induced by UCN-01 bind to the inactive form of CDK2 and prevent its phosphorylation by CAK.34) We cannot exclude the alternative possibility that UCN-01 promotes the degrada- tion of Thr160-phosphorylated CDK2 protein by an as yet unknown mechanism. Our data suggest that the contribution of the p27Kip1 pro- tein to the CDK2 inhibition by treatment with UCN-01 may be significant in the WiDr and Saos-2 cell lines (Fig. 3).
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G1-checkpoint function including a cyclin-dependent kinase 2 regulatory pathway as potential determinant of 7-hydroxystaurosporine (UCN-01)-induced apoptosis and G1-phase accumulation.
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