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A role for Cdc2- and PP2A-mediated regulation of Emi2 in the maintenance of CSF arrest.

BACKGROUND: Vertebrate oocytes are arrested in metaphase II of meiosis prior to fertilization by cytostatic factor (CSF). CSF enforces a cell-cycle arrest by inhibiting the anaphase-promoting complex (APC), an E3 ubiquitin ligase that targets Cyclin B for degradation. Although Cyclin B synthesis is ongoing during CSF arrest, constant Cyclin B levels are maintained. To achieve this, oocytes allow continuous slow Cyclin B degradation, without eliminating the bulk of Cyclin B, which would induce release from CSF arrest. However, the mechanism that controls this continuous degradation is not understood. RESULTS: We report here the molecular details of a negative feedback loop wherein Cyclin B promotes its own destruction through Cdc2/Cyclin B-mediated phosphorylation and inhibition of the APC inhibitor Emi2. Emi2 bound to the core APC, and this binding was disrupted by Cdc2/Cyclin B, without affecting Emi2 protein stability. Cdc2-mediated phosphorylation of Emi2 was antagonized by PP2A, which could bind to Emi2 and promote Emi2-APC interactions. CONCLUSIONS: Constant Cyclin B levels are maintained during a CSF arrest through the regulation of Emi2 activity. A balance between Cdc2 and PP2A controls Emi2 phosphorylation, which in turn controls the ability of Emi2 to bind to and inhibit the APC. This balance allows proper maintenance of Cyclin B levels and Cdc2 kinase activity during CSF arrest.

Pubmed ID: 17276914


  • Wu Q
  • Guo Y
  • Yamada A
  • Perry JA
  • Wang MZ
  • Araki M
  • Freel CD
  • Tung JJ
  • Tang W
  • Margolis SS
  • Jackson PK
  • Yamano H
  • Asano M
  • Kornbluth S


Current biology : CB

Publication Data

February 6, 2007

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM064348-02
  • Agency: NIGMS NIH HHS, Id: R01 GM067225
  • Agency: NIGMS NIH HHS, Id: R01 GM067225-05
  • Agency: NIGMS NIH HHS, Id: R01 GM64348
  • Agency: NIGMS NIH HHS, Id: R01 GM67225

Mesh Terms

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • CDC2 Protein Kinase
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • Cyclin B
  • DNA, Complementary
  • Enzyme Inhibitors
  • F-Box Proteins
  • Gene Library
  • Humans
  • Meiosis
  • Okadaic Acid
  • Oocytes
  • Phosphoprotein Phosphatases
  • Phosphorylation
  • Protein Binding
  • Proto-Oncogene Proteins c-mos
  • Recombinant Fusion Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Xenopus
  • Xenopus Proteins