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Cyclin A triggers mitosis either via the greatwall kinase path-way or cyclin B

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  • Nadia Hégarat
  • Adrijana Crncec
  • Maria F. Suarez Peredo Rodriguez
  • Fabio Echegaray Iturra
  • Yan Gu
  • Oliver Busby
  • Paul F. Lang
  • Alexis R. Barr
  • Chris Bakal
  • Masato T. Kanemaki
  • Angus I Lamond
  • Béla Novák
  • Tony Ly
  • Helfrid Hochegger

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Original languageEnglish
Article numbere104419
Number of pages23
JournalEMBO Journal
DOIs
Publication statusPublished - 30 Apr 2020

Abstract

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.

    Research areas

  • Cdk1, cyclin, greatwall, MASTL, PP2A

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