Reactome | CCNA:CDK1/2 complexes and CCNB1:CDK1 complexes phosphorylate FOXM1

CCNA:CDK1/2 complexes and CCNB1:CDK1 complexes phosphorylate FOXM1

Stable Identifier

R-HSA-4088024

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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CCNA:CDK1/2 complexes and CCNB1:CDK1 complexes phosphorylate FOXM1

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In the G2 phase of the cell cycle, cyclin A (CCNA) and B (CCNB)-dependent kinases CDK1 and CDK2 phosphorylate FOXM1 transcription factor, increasing its transcriptional activity. Threonine residue T611 (corresponds to T596 in FOXM1B isoform) was shown to be phosphorylated by both CCNA:CDK1/2 and CCNB:CDK1 complexes and its functional relevance is best establshed (Major et al. 2004, Laoukili et al. 2008, Fu et al. 2008). CCNA:CDK1/2 may also phosphorylate FOXM1 on T600 (Laoukili et al. 2008), while CCNB:CDK1 may phosphorylate it on S693 (S678 in FOXM1B isoform) (Fu et al. 2008). The phosphorylation of FOXM1 threonine residue T611 relieves the N-terminal domain-mediated autoinhibition of FOXM1 transcriptional activity (Laoukili et al. 2008), likely enabling interaction with transcriptional co-activators (Major et al. 2004), and creates a docking site for the Polo-box domain (PBD) of PLK1 (Fu et al. 2008).

Literature References

PubMed ID	Title	Journal	Year
15024056	Forkhead box M1B transcriptional activity requires binding of Cdk-cyclin complexes for phosphorylation-dependent recruitment of p300/CBP coactivators Major, ML, Costa, RH, Lepe, R	Mol. Cell. Biol.	2004
18285455	Activation of FoxM1 during G2 requires cyclin A/Cdk-dependent relief of autorepression by the FoxM1 N-terminal domain Medema, RH, Kleij, L, Heck, AJ, Laoukili, J, Meijer, LA, Stahl, M, Mohammed, S, Alvarez, M	Mol. Cell. Biol.	2008
19160488	Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression Fu, Z, van Deursen, JM, Li, H, Chen, J, Huang, J, Tindall, DJ, Malureanu, L, Wang, W	Nat. Cell Biol.	2008