The gene spans 25 kb and contains 10 exons.

3.4-3.6 kb mRNA; Differential splicing of exons Va (A1) and VIIa (A2) gives rise to 3 classes of transcripts, which encode 3 different protein isoforms: FoxM1A, containing both alternative exons; FoxM1B, containing none of the alternative exons and FoxM1C, containing only exon Va.

FoxM1 belongs to a large family of forkhead transcription factors. FoxM1 protein contains 3 main regions: the N-terminal Repressor Domain (NRD). This region is followed by a conserved DNA Binding Domain called Forkhead or winged-helix domain (FKH). The C-terminal region harbors the Transcativation Domain (TAD) with several activating Cyclin-Cdk-dependent phosphorylation sites.

FoxM1 is specifically expressed in proliferating cells. Expression is negatively regulated in quiescent or terminally-differentiated cells. Both expression and transcriptional activity of FoxM1 are tightly regulated during the cell cycle. Increase in FoxM1 expression levels is initiated at the onset of S-phase and continues throughout G2-phase and Mitosis. During G1 phase, FoxM1 activity is inhibited through several mechanisms, including interaction with the cell cycle inhibitory pocket protein pRb, and through inhibition by the N-terminal auto-repressor domain of FoxM1 itself. The cell cycle-inhibitory p19ARF can also bind the C-terminal transactivation domain of FoxM1 and inactivate its transcriptional activity by targeting FoxM1 protein to the nucleolus. Transcriptional activation of FoxM1 correlates with increased phosphorylation of the protein. It occurs specifically during G2-phase of the cell cycle through direct phosphorylation of the C-terminal transactivation domain (TAD) mediated by G2-Cyclin-dependent kinases (Cdks). Cyclin-Cdk-dependent phosphorylation of the C-terminal region of FoxM1 is required to relieve auto-inhibition exerted by the N-terminal repressor domain (NRD). In addition, Cdk-dependent phosphorylation of the C-terminal TAD serves to recruit transcriptional co-activators such as the histone deacetylase p300/CREB binding protein (p300/CBP). FoxM1 transcriptional activity also requires the presence of appropriate mitogenic signals involving the Raf/MEK/MAPK signaling pathway.

Nuclear, but can be detected in the cytoplasm upon inhibition of Raf/MEK/MAPK signaling. FoxM1 can also be targeted to the nucleolus by p19ARF.

FoxM1 acts as a transcriptional activator of the G2-M-specific gene cluster in mammalian cells.

Homology with other Forkhead transcription factors in the FKH DNA Binding Domain.