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

Stable Identifier
R-HSA-4088024
Type
Reaction
Species
Homo sapiens
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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
18285455 Activation of FoxM1 during G2 requires cyclin A/Cdk-dependent relief of autorepression by the FoxM1 N-terminal domain

Laoukili, J, Alvarez, M, Meijer, LA, Stahl, M, Mohammed, S, Kleij, L, Heck, AJ, Medema, RH

Mol. Cell. Biol. 2008
15024056 Forkhead box M1B transcriptional activity requires binding of Cdk-cyclin complexes for phosphorylation-dependent recruitment of p300/CBP coactivators

Major, ML, Lepe, R, Costa, RH

Mol. Cell. Biol. 2004
19160488 Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression

Fu, Z, Malureanu, L, Huang, J, Wang, W, Li, H, van Deursen, JM, Tindall, DJ, Chen, J

Nat. Cell Biol. 2008
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Catalyst Activity
Catalyst Activity
Title
cyclin-dependent protein serine/threonine kinase activity of p-CDK1/2:CCNA/p-T161-CDK1:CCNB1 [nucleoplasm]
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Activity
Orthologous Events
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Created