Dynamic Regulation of Emi2 by Emi2-Bound Cdk1/Plk1/CK1 and PP2A-B56 in Meiotic Arrest of Xenopus Eggs
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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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RSK2-mediated phosphorylation of Emi2 promotes its interaction with PP2A-B56.
“it was recently reported that RSK2-mediated phosphorylation of Emi2 promotes its well-known interaction with PP2A-B5652,53.”
From Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A (2023) · cites this paper as [53]
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Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A
Pavic, K., Gupta, N., Omella, J. D., Derua, R., Aakula, A., Huhtaniemi, R., Määttä, J. A., Höfflin, N., Okkeri, J., Wang, Z., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36693-9 · Cited by 36 · see citing works
“The data show that the CIP2A(1-560) residues cross-linked to B56α are located primarily in the N-terminal head domain (K18, K21, E23, E34, K40) with an additional residue at the C-terminus (K490) (Fig.”
BackgroundMethodInfluential
- 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
- bronze
- doi.org
- Licence
- 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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