L’équipe Pintard a publié un nouvel article dans The EMBO Journal :
The MAST kinase KIN-4 carries out mitotic entry functions of Greatwall in C. elegans
Résumé :
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.
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. The MAST kinase KIN-4 carries out mitotic entry functions of Greatwall in C. elegans. EMBO J. 2025 Feb 17. doi: 10.1038/s44318-025-00364-w. Epub ahead of print. PMID: 39962268.