Skp2-Mediated degradation of p27 regulates progression into mitosis

Keiko Nakayama, Hiroyasu Nagahama, Yohji A. Minamishima, Satoshi Miyake, Noriko Ishida, Shigetsugu Hatakeyama, Masatoshi Kitagawa, Shun ichiro Iemura, Tohru Natsume, Keiichi I. Nakayama

研究成果: ジャーナルへの寄稿記事

266 引用 (Scopus)

抄録

Although Skp2 has been thought to mediate the degradation of p27 at the G1-S transition, Skp2 -/- cells exhibit accumulation of p27 in S-G2 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 G2 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 G2-M progression by mediating the degradation of p27.

元の言語英語
ページ(範囲)661-672
ページ数12
ジャーナルDevelopmental Cell
6
発行部数5
DOI
出版物ステータス出版済み - 5 1 2004

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Mitosis
Degradation
G2 Phase
Proteolysis
Phenotype
Phosphotransferases
Chemical activation
S Phase
Cell Division
Hepatocytes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

これを引用

Nakayama, K., Nagahama, H., Minamishima, Y. A., Miyake, S., Ishida, N., Hatakeyama, S., ... Nakayama, K. I. (2004). Skp2-Mediated degradation of p27 regulates progression into mitosis. Developmental Cell, 6(5), 661-672. https://doi.org/10.1016/S1534-5807(04)00131-5

Skp2-Mediated degradation of p27 regulates progression into mitosis. / Nakayama, Keiko; Nagahama, Hiroyasu; Minamishima, Yohji A.; Miyake, Satoshi; Ishida, Noriko; Hatakeyama, Shigetsugu; Kitagawa, Masatoshi; Iemura, Shun ichiro; Natsume, Tohru; Nakayama, Keiichi I.

:: Developmental Cell, 巻 6, 番号 5, 01.05.2004, p. 661-672.

研究成果: ジャーナルへの寄稿記事

Nakayama, K, Nagahama, H, Minamishima, YA, Miyake, S, Ishida, N, Hatakeyama, S, Kitagawa, M, Iemura, SI, Natsume, T & Nakayama, KI 2004, 'Skp2-Mediated degradation of p27 regulates progression into mitosis', Developmental Cell, 巻. 6, 番号 5, pp. 661-672. https://doi.org/10.1016/S1534-5807(04)00131-5
Nakayama K, Nagahama H, Minamishima YA, Miyake S, Ishida N, Hatakeyama S その他. Skp2-Mediated degradation of p27 regulates progression into mitosis. Developmental Cell. 2004 5 1;6(5):661-672. https://doi.org/10.1016/S1534-5807(04)00131-5
Nakayama, Keiko ; Nagahama, Hiroyasu ; Minamishima, Yohji A. ; Miyake, Satoshi ; Ishida, Noriko ; Hatakeyama, Shigetsugu ; Kitagawa, Masatoshi ; Iemura, Shun ichiro ; Natsume, Tohru ; Nakayama, Keiichi I. / Skp2-Mediated degradation of p27 regulates progression into mitosis. :: Developmental Cell. 2004 ; 巻 6, 番号 5. pp. 661-672.
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abstract = "Although Skp2 has been thought to mediate the degradation of p27 at the G1-S transition, Skp2 -/- cells exhibit accumulation of p27 in S-G2 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 G2 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 G2-M progression by mediating the degradation of p27.",
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AU - Nakayama, Keiichi I.

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