論文 - 詳細
| RRC ID | 84193 |
|---|---|
| 著者 | Roumbo L, Ossareh-Nazari B, Vigneron S, Stefani I, Van Hove L, Legros V, Chevreux G, Lacroix B, Castro A, Joly N, Lorca T, Pintard L. |
| タイトル | The MAST kinase KIN-4 carries out mitotic entry functions of Greatwall in C. elegans. |
| ジャーナル | EMBO J |
| Abstract |
MAST-like, or Greatwall (Gwl), an atypical protein kinase related to the evolutionarily conserved MAST kinase family, is crucial for cell cycle control during mitotic entry. Mechanistically, Greatwall is activated by Cyclin B-Cdk1 phosphorylation of a 550 amino acids-long insertion in its atypical activation segment. Subsequently, Gwl phosphorylates Endosulfine and Arpp19 to convert them into inhibitors of PP2A-B55 phosphatase, thereby preventing early dephosphorylation of M-phase targets of Cyclin B-Cdk1. Here, searching for an elusive Gwl-like activity in C. elegans, we show that the single worm MAST kinase, KIN-4, fulfills this function in worms and can functionally replace Greatwall in the heterologous Xenopus system. Compared to Greatwall, the short activation segment of KIN-4 lacks a phosphorylation site, and KIN-4 is active even when produced in E. coli. We also show that a balance between Cyclin B-Cdk1 and PP2A-B55 activity, regulated by KIN-4, is essential to ensure asynchronous cell divisions in the early worm embryo. These findings resolve a long-standing puzzle related to the supposed absence of a Greatwall pathway in C. elegans, and highlight a novel aspect of PP2A-B55 regulation by MAST kinases. |
| 巻・号 | 44(7) |
| ページ | 1943-1974 |
| 公開日 | 2025-4-1 |
| DOI | 10.1038/s44318-025-00364-w |
| PII | 10.1038/s44318-025-00364-w |
| PMID | 39962268 |
| PMC | PMC11961639 |
| MeSH | Animals CDC2 Protein Kinase / metabolism Caenorhabditis elegans* / cytology Caenorhabditis elegans* / embryology Caenorhabditis elegans* / enzymology Caenorhabditis elegans* / genetics Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cyclin B / metabolism Mitosis* / physiology Phosphorylation Protein Phosphatase 2 / metabolism Protein Serine-Threonine Kinases* / genetics Protein Serine-Threonine Kinases* / metabolism Xenopus laevis |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 16 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm2810 tm1049 |