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

4 Citations (Scopus)
46 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
Pages (from-to)1-23
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

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