PP2Cγ‐mediated S‐phase accumulation induced by the proteasome‐dependent degradation of p21WAF1/CIP1

Abstract
Serine/threonine phosphatases such as PP1, PP2A, and PP2B are well known to regulate the transition phase of the cell cycle. However, the function of PP2C gamma in cell cycle progression is still unclear. In the present study, we report the characterization of PP2C gamma in mammalian cells during the cell cycle. After release of synchronized cells from thymidine block, overexpression of PP2C gamma led to accumulation in the S phase. The amount of endogenous p21(WAF1/CIP1) protein was markedly reduced by the expression of PP2C gamma. The degradation of p21(WAF1/CIP1) induced by PP2C gamma was mediated in a proteasome-dependent manner. In addition, the phosphatase activity of PP2C gamma was capable of repressing the level of p21(WAF1/CIP1) protein. Phosphorylation of Rb was also reduced in cells expressing PP2C gamma. Taken together, these results indicate that PP2C gamma-induced S phase accumulation may be associated with proteasome-directed p21(WAF1/CIP1) degradation. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.