First Author | Nakayama K | Year | 2004 |
Journal | Dev Cell | Volume | 6 |
Issue | 5 | Pages | 661-72 |
PubMed ID | 15130491 | Mgi Jnum | J:90569 |
Mgi Id | MGI:3044236 | Doi | 10.1016/s1534-5807(04)00131-5 |
Citation | Nakayama K, et al. (2004) Skp2-mediated degradation of p27 regulates progression into mitosis. Dev Cell 6(5):661-72 |
abstractText | Although Skp2 has been thought to mediate the degradation of p27 at the G(1)-S transition, Skp2(-/-) cells exhibit accumulation of p27 in S-G(2) phase with overreplication. We demonstrate that Skp2(-/-)p27(-/-) mice do not exhibit the overreplication phenotype, suggesting that p27 accumulation is required for its development. Hepatocytes of Skp2(-/-) mice entered the endoduplication cycle after mitogenic stimulation, whereas this phenotype was not apparent in Skp2(-/-)p27(-/-) mice. Cdc2-associated kinase activity was lower in Skp2(-/-) cells than in wild-type cells, and a reduction in Cdc2 activity was sufficient to induce overreplication. The lack of p27 degradation in G(2) phase in Skp2(-/-) cells may thus result in suppression of Cdc2 activity and consequent inhibition of entry into M phase. These data suggest that p27 proteolysis is necessary for the activation of not only Cdk2 but also Cdc2, and that Skp2 contributes to regulation of G(2)-M progression by mediating the degradation of p27. |