Chk1 is activated transiently and targets Cdc25A for degradation at the Xenopus midblastula transition

Ken Shimuta, Nobushige Nakajo, Katsuhiro Uto, Yoshimasa Hayano, Kenji Okazaki, Noriyuki Sagata

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

In Xenopus embryos, cell cycle elongation and degradation of Cdc25A (a Cdk2 Tyr15 phosphatase) occur naturally at the midblastula transition (MBT), at which time a physiological DNA replication checkpoint is thought to be activated by the exponentially increased nucleo-cytoplasmic ratio. Here we show that the checkpoint kinase Chk1, but not Cds1 (Chk2), is activated transiently at the MBT in a maternal/zygotic gene product-regulated manner and is essential for cell cycle elongation and Cdc25A degradation at this transition. A constitutively active form of Chk1 can phosphorylate Cdc25A in vitro and can target it rapidly for degradation in pre-MBT embryos. Intriguingly, for this degradation, however, Cdc25A also requires a prior Chk1-independent phosphorylation at Ser73. Ectopically expressed human Cdc25A can be degraded in the same way as Xenopus Cdc25A. Finally, Cdc25A degradation at the MBT is a prerequisite for cell viability at later stages. Thus, the physiological replication checkpoint is activated transiently at the MBT by developmental cues, and activated Chkl, only together with an unknown kinase, targets Cdc25A for degradation to ensure later development.

Original languageEnglish
Pages (from-to)3694-3703
Number of pages10
JournalEMBO Journal
Volume21
Issue number14
DOIs
Publication statusPublished - Jul 15 2002

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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