Cyclin A triggers Mitosis either via the Greatwall kinase pathway or Cyclin B

Nadia Hegarat, Adrijana Crncec, Maria F. Suarez Peredoa Rodriguez, Fabio Echegaray Iturra, Yan Gu, Oliver Busby, Paul F. Lang, Alexis R. Barr, Chris Bakal, Masato T. Kanemaki, Angus I. Lamond, Bela Novak, Tony Ly (Lead / Corresponding author), Helfrid Hochegger (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    41 Citations (Scopus)
    144 Downloads (Pure)

    Abstract

    Two mitotic cyclin types, cyclin A and B, exist in higher eukaryotes, but their specialised functions in mitosis are incompletely understood. Using degron tags for rapid inducible protein removal, 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 decisive 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 Greatwall kinase coordinate mitotic progression by increasing levels of Cdk1-dependent substrate phosphorylation.

    Original languageEnglish
    Article numbere104419
    Number of pages23
    JournalEMBO Journal
    Volume39
    Issue number11
    Early online date30 Apr 2020
    DOIs
    Publication statusPublished - 2 Jun 2020

    Keywords

    • Cdk1
    • Cyclin
    • Greatwall
    • MASTL
    • PP2A

    ASJC Scopus subject areas

    • General Biochemistry,Genetics and Molecular Biology
    • General Immunology and Microbiology
    • Molecular Biology
    • General Neuroscience

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