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 language | English |
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Article number | e104419 |
Number of pages | 23 |
Journal | EMBO Journal |
Volume | 39 |
Issue number | 11 |
Early online date | 30 Apr 2020 |
DOIs | |
Publication status | Published - 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