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

Published

Journal Article

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.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.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