Protein phosphatase 2Cgamma regulates the level of p21Cip1/WAF1 by Akt signaling.
PP2Cgamma 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 p21(Cip1/WAF1)was affected by PP2Cgamma, causing an accumulation of cells in S phase. Here, we demonstrate that the PP2Cgamma-induced degradation of p21(Cip1/WAF1) is mediated by Akt signaling. In cells expressing PP2Cgamma, Akt1 protein was phosphorylated. When PP2Cgamma expression was knocked down, the phosphorylation of Akt1 was reduced and the level of p21(Cip1/WAF1) protein was increased. Interestingly, the stability of p21(Cip1/WAF1) was highly maintained in Akt1-depleted cells despite the ectopic expression of PP2Cgamma. Taken together, these results suggest that PP2Cgamma is a novel regulator of p21(Cip1/WAF1) protein stability via the Akt signaling pathway.
Suh
Eun-Jung
EJ
Department of Biology, Kyung Hee University, 1 Hoegi-dong Dongdaemoon-ku, Seoul 130-701, Republic of Korea.
Kim
Yoon-Jin
YJ
Kim
Sang Hoon
SH
D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D000071636:Protein Phosphatase 2C; D055550:Protein Stability; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051057:Proto-Oncogene Proteins c-akt; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C