Cyclin A triggers Mitosis either via the Greatwall kinase pathway or Cyclin B.pdf (3.87 MB)
Cyclin A triggers Mitosis either via the Greatwall kinase pathway or Cyclin B
journal contribution
posted on 2023-06-07, 07:26 authored by Nadia Hegarat, Adrijana Crncec, Maria Fernanda Suarez Peredo Rodriguez, Fabio Rodrigo Echegaray Iturra, Yan Gu, Oliver Busby, Paul F Lang, Alexis R Barr, Chris Bakal, Masato T Kanemaki, Angus I Lamond, Bela Novak, Tony Ly, Helfrid HocheggerHelfrid HocheggerTwo 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.
History
Publication status
- Published
File Version
- Published version
Journal
EMBO JournalISSN
0261-4189Publisher
EMBO PressExternal DOI
Issue
11Volume
39Page range
1-23Article number
a104419Event location
EnglandDepartment affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes