Cyclin A2 is a key regulator of the cell cycle, implicated both in DNA replication and mitotic entry. Cyclin A2 participates in feedback loops that activate mitotic kinases in G2 phase, but why active Cyclin A2-CDK2 during the S phase does not trigger mitotic kinase activation remains unclear. Here, we describe a change in localisation of Cyclin A2 from being only nuclear to both nuclear and cytoplasmic at the S/G2 border. We find that Cyclin A2-CDK2 can activate the mitotic kinase PLK1 through phosphorylation of Bora, and that only cytoplasmic Cyclin A2 interacts with Bora and PLK1. Expression of predominately cytoplasmic Cyclin A2 or phospho-mimicking PLK1 T210D can partially rescue a G2 arrest caused by Cyclin A2 depletion. Cytoplasmic presence of Cyclin A2 is restricted by p21, in particular after DNA damage. Cyclin A2 chromatin association during DNA replication and additional mechanisms contribute to Cyclin A2 localisation change in the G2 phase. We find no evidence that such mechanisms involve G2 feedback loops and suggest that cytoplasmic appearance of Cyclin A2 at the S/G2 transition functions as a trigger for mitotic kinase activation.
- MeSH
- aktivace enzymů genetika MeSH
- buněčné jádro metabolismus MeSH
- chromatin metabolismus MeSH
- cyklin A2 genetika metabolismus MeSH
- cyklin-dependentní kinasa 2 nedostatek genetika MeSH
- cytoplazma metabolismus MeSH
- fosforylace genetika MeSH
- G2 fáze genetika MeSH
- HeLa buňky MeSH
- lidé MeSH
- mitóza genetika MeSH
- poškození DNA genetika MeSH
- protein-serin-threoninkinasy metabolismus MeSH
- proteinkinasa CDC2 nedostatek genetika MeSH
- proteiny buněčného cyklu metabolismus MeSH
- protoonkogenní proteiny metabolismus MeSH
- S fáze genetika MeSH
- signální transdukce genetika MeSH
- transfekce MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
