1. A role for Cdc2- and PP2A-mediated regulation of Emi2 in the maintenance of CSF arrest.
- Author
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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, and Kornbluth S
- Subjects
- Anaphase-Promoting Complex-Cyclosome, Animals, Cdc20 Proteins, Cell Cycle Proteins metabolism, Cyclin B metabolism, DNA, Complementary, Enzyme Inhibitors pharmacology, Gene Library, Humans, Meiosis, Okadaic Acid pharmacology, Oocytes metabolism, Phosphorylation, Protein Binding drug effects, Recombinant Fusion Proteins metabolism, Ubiquitin-Protein Ligase Complexes metabolism, Xenopus, CDC2 Protein Kinase metabolism, F-Box Proteins metabolism, Oocytes cytology, Phosphoprotein Phosphatases metabolism, Proto-Oncogene Proteins c-mos metabolism, Xenopus Proteins metabolism
- Abstract
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.
- Published
- 2007
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