Cited by 42Microtubule and mitosis dynamicsCancer-related Molecular PathwaysUbiquitin and proteasome pathways

Dynamic Regulation of Emi2 by Emi2-Bound Cdk1/Plk1/CK1 and PP2A-B56 in Meiotic Arrest of Xenopus Eggs

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Isoda, Michitaka, Sako, Kosuke, Suzuki, Kazuhiro, Nishino, Kazuaki, Nakajo, Nobushige, Ohe, Munemichi, Ezaki, Takanori, Kanemori, Yoshinori +3 more·2011·Developmental Cell

Abstract

In vertebrates, unfertilized eggs are arrested at metaphase of meiosis II by Mos and Emi2, an inhibitor of the APC/C ubiquitin ligase. In Xenopus, Cdk1 phosphorylates Emi2 and both destabilizes and inactivates it, whereas Mos recruits PP2A phosphatase to antagonize the Cdk1 phosphorylation. However, how Cdk1 phosphorylation inhibits Emi2 is largely unknown. Here we show that multiple N-terminal Cdk1 phosphorylation motifs bind cyclin B1-Cdk1 itself, Plk1, and CK1δ/ε to inhibit Emi2. Plk1, after rebinding to other sites by self-priming phosphorylation, partially destabilizes Emi2. Cdk1 and CK1δ/ε sequentially phosphorylate the C-terminal APC/C-docking site, thereby cooperatively inhibiting Emi2 from binding the APC/C. In the presence of Mos, however, PP2A-B56β/ε bind to Emi2 and keep dephosphorylating it, particularly at the APC/C-docking site. Thus, Emi2 stability and activity are dynamically regulated by Emi2-bound multiple kinases and PP2A phosphatase. Our data also suggest a general role for Cdk1 substrate phosphorylation motifs in M phase regulation.

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Crossref · 10.1016/j.devcel.2011.06.029

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Authors
Isoda, M., Sako, K., Suzuki, K., Nishino, K., Nakajo, N., Ohe, M., Ezaki, T., Kanemori, Y., Inoue, D., Ueno, H., & Sagata, N.
Affiliations
Kyushu University (JP)
Corresponding author
Sagata, Noriyuki
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2011-09
Volume
21
Issue
3
Pages
506-519
ISSN
1534-5807 (ISSN-L)
OpenAlex
W2021659737
Cited by
42
References
48
Citations by year
2025: 4 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 2 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 4 · 2012: 4
FWCI
1.99
Type
journal article
Language
en
Open access
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
Emi2, CDK1 phosphorylation, PLK1, PP2A-B56, MOS, meiotic arrest, metaphase II, Xenopus eggs, protein stability, protein dephosphorylation
MeSH terms
Polo-Like Kinase 1, Animals, Cell Division, Female, Meiosis, Ovum, Phosphorylation, Proto-Oncogene Proteins, Xenopus laevis, CDC2 Protein Kinase, Proto-Oncogene Proteins c-mos, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Xenopus Proteins, F-Box Proteins, Casein Kinase I, Protein Phosphatase 2, Protein Interaction Domains and Motifs

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