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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • February 2007

Published In

Volume / Issue

  • 17 / 3

Start / End Page

  • 213 - 224

PubMed ID

  • 17276914

Pubmed Central ID

  • 17276914

Electronic International Standard Serial Number (EISSN)

  • 1879-0445

International Standard Serial Number (ISSN)

  • 0960-9822

Digital Object Identifier (DOI)

  • 10.1016/j.cub.2006.12.045

Language

  • eng