Cdc2 and Mos regulate Emi2 stability to promote the meiosis I-meiosis II transition.
The transition of oocytes from meiosis I (MI) to meiosis II (MII) requires partial cyclin B degradation to allow MI exit without S phase entry. Rapid reaccumulation of cyclin B allows direct progression into MII, producing a cytostatic factor (CSF)-arrested egg. It has been reported that dampened translation of the anaphase-promoting complex (APC) inhibitor Emi2 at MI allows partial APC activation and MI exit. We have detected active Emi2 translation at MI and show that Emi2 levels in MI are mainly controlled by regulated degradation. Emi2 degradation in MI depends not on Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), but on Cdc2-mediated phosphorylation of multiple sites within Emi2. As in MII, this phosphorylation is antagonized by Mos-mediated recruitment of PP2A to Emi2. Higher Cdc2 kinase activity in MI than MII allows sufficient Emi2 phosphorylation to destabilize Emi2 in MI. At MI anaphase, APC-mediated degradation of cyclin B decreases Cdc2 activity, enabling Cdc2-mediated Emi2 phosphorylation to be successfully antagonized by Mos-mediated PP2A recruitment. These data suggest a model of APC autoinhibition mediated by stabilization of Emi2; Emi2 proteins accumulate at MI exit and inhibit APC activity sufficiently to prevent complete degradation of cyclin B, allowing MI exit while preventing interphase before MII entry.
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Wanli
W
Tang
Judy Qiju
JQ
Wu
Yanxiang
Y
Guo
David V
DV
Hansen
Jennifer A
JA
Perry
Christopher D
CD
Freel
Leta
L
Nutt
Peter K
PK
Jackson
Sally
S
Kornbluth
D000818:Animals; D016203:CDC2 Protein Kinase; D002465:Cell Movement; D019926:Cyclin B / Q000378:metabolism / Q000502:physiology*; D018844:Cyclin-Dependent Kinases; D004705:Endocytosis; D044783:F-Box Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism; D017231:Proto-Oncogene Proteins c-mos / Q000378:metabolism / Q000502:physiology*
D019926:Cyclin B; C509434:Emi2 protein, mouse; D044783:F-Box Proteins; C533792:FBXO43 protein, human; D017231:Proto-Oncogene Proteins c-mos; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases