Meta-Biol

• Pathways

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).