Emi2 mediates meiotic MII arrest by competitively inhibiting the binding of Ube2S to the APC/C
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Updated: Apr 30, 2026
In Vitro Biochemical Assays using Biotin Labels to Study Protein-Nucleic Acid Interactions
Published on: July 17, 2019
Kosuke Sako1, Kazuhiro Suzuki1, Michitaka Isoda2
1Department of Biology, Graduate School of Sciences, Kyushu University, Hakozaki 6-10-1, Fukuoka 812-8581, Japan.
Abstract:
In vertebrates, unfertilized eggs are arrested at metaphase of meiosis II by Emi2, a direct inhibitor of the APC/C ubiquitin ligase. Two different ubiquitin-conjugating enzymes, UbcH10 and Ube2S, work with the APC/C to target APC/C substrates for degradation. However, their possible roles and regulations in unfertilized/fertilized eggs are not known. Here we use Xenopus egg extracts to show that both UbcH10 and Ube2S are required for rapid cyclin B degradation at fertilization, when APC/C binding of Ube2S, but not of UbcH10, increases several fold, coincidently with (SCF(β-TrCP)-dependent) Emi2 degradation. Interestingly, before fertilization, Emi2 directly inhibits APC/C-Ube2S binding via the C-terminal tail, but on fertilization, its degradation allows the binding mediated by the Ube2S C-terminal tail. Significantly, Emi2 and Ube2S bind commonly to the APC/C catalytic subunit APC10 via their similar C-terminal tails. Thus, Emi2 competitively inhibits APC/C-Ube2S binding before fertilization, while its degradation on fertilization relieves the inhibition for APC/C activation.
Insights
Emi2 inhibits the APC/C ubiquitin ligase in unfertilized eggs. Its degradation upon fertilization allows Ube2S binding, activating the APC/C for cell cycle progression.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Unfertilized vertebrate eggs arrest at meiosis II via Emi2 inhibition of the APC/C ubiquitin ligase.
- UbcH10 and Ube2S are ubiquitin-conjugating enzymes that function with APC/C, but their roles in eggs are unclear.
Purpose of the Study:
- To investigate the roles and regulation of UbcH10 and Ube2S in unfertilized and fertilized Xenopus egg extracts.
- To elucidate the mechanism by which Emi2 regulates APC/C activity during fertilization.
Main Methods:
- Utilized Xenopus egg extracts to study protein degradation and enzyme binding dynamics.
- Analyzed changes in APC/C binding of UbcH10 and Ube2S upon fertilization.
- Investigated the interaction between Emi2, Ube2S, and APC/C subunits.
Main Results:
- Both UbcH10 and Ube2S are essential for rapid cyclin B degradation during fertilization.
- APC/C binding of Ube2S, but not UbcH10, significantly increases post-fertilization, coinciding with Emi2 degradation.
- Emi2 directly inhibits APC/C-Ube2S binding via its C-terminal tail; Emi2 degradation relieves this inhibition.
Conclusions:
- Emi2 competitively inhibits APC/C-Ube2S binding before fertilization.
- Degradation of Emi2 upon fertilization enables Ube2S-mediated APC/C activation, crucial for cell cycle progression.
- Emi2 and Ube2S share a common binding site on APC10, highlighting a competitive inhibition mechanism.
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