A Role for Cdc2- and PP2A-Mediated Regulation of Emi2 in the Maintenance of CSF Arrest

Wu, Qiju; Guo, Yanxiang; Yamada, Ayumi; Perry, Jennifer A.; Wang, Michael Z.; Araki, Marito; Freel, Christopher D.; Tung, Jeffrey J.; Tang, Wanli; Margolis, Seth S.; Jackson, Peter K.; Yamano, Hiroyuki; Asano, Maki; Kornbluth, Sally

doi:10.1016/j.cub.2006.12.045

Cited by 45 publications

(79 citation statements)

References 39 publications

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“…With Mos promoting its dephosphorylation, Emi2 is stabilized and accumulates, resulting in APC inhibition, which is necessary for S phase block and MII entry. In MII, Cdc2 kinase activity remains relatively low as compared with MI through an APC-mediated feedback loop we reported previously (Wu et al, 2007b). Emi2 is stable in MII, which is essential for CSF arrest.…”

Section: An Autoinhibitory Loop Regulates Apc Activity During the Mi-mentioning

confidence: 57%

“…Emi2 mutants including S213A/T239A/T252A/T267A, T545/551A, DS32AA, and T195A were cloned as previously described (Wu et al, 2007b), as were the Myc 6 -tagged Emi2 open reading frame (ORF), including its own 3Ј-untranslated region (UTR; WT and DS32AA) in pCS2ϩ vector (Tung et al, 2007). For mRNA synthesis, Emi2 ORFs (Emi2 aa 489-651, Emi2 wild-type, Emi2 DS32AA, and Emi2 4A) were PCR amplified and subcloned into the NotI site of the pSP64T vector.…”

Section: Cloning Protein Expression and Mrna Preparationmentioning

confidence: 99%

“…As shown in Figure 1C, Emi2 was quickly degraded after GVBD in progesterone-treated oocytes, but remained stable in the untreated controls. To demonstrate the relevance of Emi2 regulation in the MI-MII transition, we injected oocytes with Emi2 (489-651) mRNA encoding a fragment of Emi2 known to be nondegradable in MII, but able to inhibit the APC (Wu et al, 2007b). In control oocytes (either uninjected or injected with ␤-globin control mRNA), cyclin B degradation, indicative of APC activation, occurred approximately 2 h after visual GVBD, though it was not complete (as is characteristic of the MI-MII boundary).…”

Section: Tight Regulation Of Emi2 Levels Is Critical For Ensuring a Smentioning

confidence: 99%

“…Because our previous work demonstrated that this Cdc2-mediated pathway could also be operative during an MII arrest (Wu et al, 2007b), we were left with the perplexing question of why Emi2 was maintained at a level sufficient to produce an arrest in MII, but not in MI. We initially hypothesized that this difference might reflect differential activity of Mos or its (D) Left, oocytes were first injected with Myc 6 -Emi2-3Ј-UTR mRNA (11 pg/oocyte).…”

Section: Differential Emi2 Stability In MI and Mii Is Controlled By Dmentioning

confidence: 99%

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Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

Tang

Guo

et al. 2008

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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 Ca2+/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.

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Section: An Autoinhibitory Loop Regulates Apc Activity During the Mi-mentioning

confidence: 57%

Section: Cloning Protein Expression and Mrna Preparationmentioning

confidence: 99%

Section: Tight Regulation Of Emi2 Levels Is Critical For Ensuring a Smentioning

confidence: 99%

Section: Differential Emi2 Stability In MI and Mii Is Controlled By Dmentioning

confidence: 99%

See 2 more Smart Citations

Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

Tang

Guo

et al. 2008

MBoC

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“…An inhibitor of APC/C called early mitotic inhibitor 2 (Emi2; also known as Erp1) was recently shown to be a key component of CSF in both frog and mouse eggs (8)(9)(10). Binding of Emi2 to APC/C blocks substrate binding and inhibits its ligase activity (11). Addition of Emi2 to cycling extracts results in a mitotic arrest with the stabilization of cyclin B (8,9).…”

mentioning

confidence: 99%