Chk1, but not Chk2, inhibits Cdc25 phosphatases by a novel common mechanism

Katsuhiro Uto, Daigo Inoue, Ken Shimuta, Nobushige Nakajo, Noriyuki Sagata

研究成果: ジャーナルへの寄稿学術誌査読

87 被引用数 (Scopus)

抄録

Cdc25 phosphatases activate cyclin-dependent kinases (Cdks) and thereby promote cell cycle progression. In vertebrates, Chk1 and Chk2 phosphorylate Cdc25A at multiple N-terminal sites and target it for rapid degradation in response to genotoxic stress. Here we show that Chk1, but not Chk2, phosphorylates Xenopus Cdc25A at a novel C-terminal site (Thr504) and inhibits it from C-terminally interacting with various Cdk-cyclin complexes, including Cdk1-cyclin A, Cdk1-cyclin B, and Cdk2-cyclin E. Strikingly, this inhibition, rather than degradation itself, of CdcZSA is essential for the Chk1-induced cell cycle arrest and the DNA replication checkpoint in early embryos. 14-3-3 proteins bind to Chk1-phosphorylated Thr504, but this binding is not required for the inhibitory effect of Thr504 phosphorylation. A C-terminal site presumably equivalent to Thr504 exists in all known Cdc25 family members from yeast to humans, and its phosphorylation by Chk1 (but not Chk2) can also inhibit all examined Cdc25 family members from C-terminally interacting with their Cdk-cyclin substrates. Thus, Chk1 but not Chk2 seems to inhibit virtually all Cdc25 phosphatases by a novel common mechanism.

本文言語英語
ページ(範囲)3386-3396
ページ数11
ジャーナルEMBO Journal
23
16
DOI
出版ステータス出版済み - 8月 18 2004

!!!All Science Journal Classification (ASJC) codes

  • 神経科学一般
  • 分子生物学
  • 生化学、遺伝学、分子生物学一般
  • 免疫学および微生物学一般

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