ArticleProceedings of the National Academy of Sciences of the United States of America2006
CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- The degradation of maternal RNA-binding protein 4E-T regulates translational activation to ensure maternal-to-zygotic transition in mouse embryos.Cellular and molecular life sciences : CMLS · 2026Article
- Rescuing Fertilization Failure in ICSI: A Narrative Review of Calcium Ionophore Activation, PLCζ Testing, and Embryo Morphokinetics.Biomedicines · 2025Review
- Decoding protein phosphorylation during oocyte meiotic divisions using phosphoproteomics.eLife · 2025Article
- Egg Overactivation-An Overlooked Phenomenon of Gamete Physiology.International journal of molecular sciences · 2025Review
- No transcription, no problem: Protein phosphorylation changes and the transition from oocyte to embryo.Current topics in developmental biology · 2025Review
- CaMKII suppresses proteotoxicity by phosphorylating BAG3 in response to proteasomal dysfunction.EMBO reports · 2024Article
- Molecular Mechanism of Oocyte Activation in Mammals: Past, Present, and Future Directions.Biomolecules · 2024Review
- Calcium signaling in oocyte quality and functionality and its application.Frontiers in endocrinology · 2024Review
- Meiotic Cell Cycle Progression in Mouse Oocytes: Role of Cyclins.International journal of molecular sciences · 2023Review
- Review
- Article
- Integrated multiple transcriptomes in oviductal tissue across the porcine estrous cycle reveal functional roles in oocyte maturation and transport.Journal of animal science · 2022Article
- Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA.Journal of translational medicine · 2021Article
- EMI2 expression as a poor prognostic factor in patients with breast cancer.The Kaohsiung journal of medical sciences · 2020Article
- Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay.Journal of visualized experiments : JoVE · 2018Article
- Post-translational regulation of the maternal-to-zygotic transition.Cellular and molecular life sciences : CMLS · 2018Review
- Postovulatory cell death: why eggs die via apoptosis in biological species with external fertilization.The Journal of reproduction and development · 2018Review
- Proteomics of phosphorylation and protein dynamics during fertilization and meiotic exit in theProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Differing molecular response of young and advanced maternal age human oocytes to IVM.Human reproduction (Oxford, England) · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In vertebrate meiosis, unfertilized eggs are arrested in metaphase II by cytostatic factor (CSF), which is required to maintain mitotic cyclin-dependent kinase activity. Fertilization triggers a transient increase in cytosolic free Ca(2+), which leads to CSF inactivation and ubiquitin-dependent cyclin destruction through the anaphase promoting complex or cyclosome (APC/C). The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and the Polo-like kinase Plx1 are essential factors for Ca(2+)-induced meiotic exit, but the critical targets of these kinases were unknown. The APC/C inhibitor Emi2 or XErp1 has recently been characterized as a pivotal CSF component, required to maintain metaphase II arrest and rapidly destroyed in response to Ca(2+) signaling through phosphorylation by Plx1 and ubiquitination by the SCF(betaTrCP) complex. An important question is how the increase in free Ca(2+) targets Plx1 activity toward Emi2. Here, we demonstrate that CaMKII is required for Ca(2+)-induced Emi2 destruction, and that CaMKII functions as a "priming kinase," directly phosphorylating Emi2 at a specific motif to induce a strong interaction with the Polo Box domain of Plx1. We show that the strict requirement for CaMKII to phosphorylate Emi2 is a specific feature of CSF arrest, and we also use phosphatase inhibitors to demonstrate an additional mode of Emi2 inactivation independent of its destruction. We firmly establish the CSF component Emi2 as the first-known critical and direct target of CaMKII in CSF release, providing a detailed molecular mechanism explaining how CaMKII and Plx1 coordinately direct APC/C activation and meiotic exit upon fertilization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.