Zdroj: |
Hégarat, N, Crncec, A, Suarez Peredo Rodriguez, M F, Echegaray Iturra, F, Gu, Y, Busby, O, Lang, P F, Barr, A R, Bakal, C, Kanemaki, M T, Lamond, A I, Novák, B, Ly, T & Hochegger, H 2020, ' Cyclin A triggers mitosis either via the greatwall kinase path-way or cyclin B ', EMBO Journal . https://doi.org/10.15252/embj.202010441 |
Popis: |
Two mitotic cyclin types, cyclin A and B, exist in higher eukaryotes, but their specialised func-tions in mitosis are incompletely understood. Using degron tags for rapid inducible protein remov-al, we analyse how acute depletion of these proteins affects mitosis. Loss of cyclin A in G2-phase prevents mitotic entry. Cells lacking cyclin B can enter mitosis and phosphorylate most mitotic proteins, because of parallel PP2A:B55 phosphatase inactivation by Greatwall kinase. The final barrier to mitotic establishment corresponds to nuclear envelope breakdown, which requires a de-cisive shift in the balance of cyclin-dependent kinase Cdk1 and PP2A:B55 activity. Beyond this point, cyclin B/Cdk1 is essential for phosphorylation of a distinct subset of mitotic Cdk1 substrates that are essential to complete cell division. Our results identify how cyclin A, cyclin B and Great-wall kinase coordinate mitotic progression by increasing levels of Cdk1-dependent substrate phos-phorylation. |