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

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 PP2Cγ in cell cycle progression is still unclear. In the present study, we report the characterization of PP2Cγ in mammalian cells during the cell cycle. After release of synchronized cells from thymidine block, over-expression of PP2Cγ led to accumulation in the S phase. The amount of endogenous p21WAF1/CIP1 protein was markedly reduced by the expression of PP2Cγ. The degradation of p21WAF1/CIP1 induced by PP2Cγ was mediated in a proteasome-dependent manner. In addition, the phosphatase activity of PP2Cγ was capable of repressing the level of p21WAF1/CIP1 protein. Phosphorylation of Rb was also reduced in cells expressing PP2Cγ. Taken together, these results indicate that PP2Cγ-induced S phase accumulation may be associated with proteasome-directed p21WAF1/CIP1 degradation.