Protein phosphatase 2Cγ regulates the level of p21Cip1/WAF1 by Akt signaling

PP2Cγ is a splicing factor that dephosphorylates specific substrates required for the formation of the spliceosome. In a previous study, we reported that the degradation of p21Cip1/WAF1was affected by PP2Cγ, causing an accumulation of cells in S phase. Here, we demonstrate that the PP2Cγ-induced degradation of p21Cip1/WAF1 is mediated by Akt signaling. In cells expressing PP2Cγ, Akt1 protein was phosphorylated. When PP2Cγ expression was knocked down, the phosphorylation of Akt1 was reduced and the level of p21Cip1/WAF1 protein was increased. Interestingly, the stability of p21Cip1/WAF1 was highly maintained in Akt1-depleted cells despite the ectopic expression of PP2Cγ. Taken together, these results suggest that PP2Cγ is a novel regulator of p21Cip1/WAF1 protein stability via the Akt signaling pathway.