FOXM1 (forkhead box M1)

2008-02-01   Jamila Laoukili , Monica Alvarez Fernandez , René H Medema 

Department of Human Genetics, Academic Medical Center, Amsterdam, The Netherlands (JL); Department of Medical Oncology, University Medical Center Utrecht, The Netherlands (MAF, RHM)




Atlas Image


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.


Atlas Image


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.

Implicated in

Entity name
FoxM1 is commonly upregulated in human aggressive carcinomas originating from prostate, breast, lung, ovary, colon, pancreas, stomach, bladder, liver and kidney. FoxM1 promotes tumor progression of prostate carcinomas and lung adenocarcinomas. FoxM1 expression and activity are significantly elevated in basal cell carcinoma (BCC) skin tumors and FoxM1 expression in malignant gliomas correlates with disease staging. FoxM1 contributes to cellular transformation by the high-risk human papillomavirus-16 (HPV-16) E7 protein. Conditional deletion of the FoxM1 gene in mice reduces proliferation of lung tumors and renders hepatocytes resistant to tumor development. Down-regulation of FoxM1 reduces the invasiveness of glioma cells and decreases cell migration and cell invasion in pancreatic cancer cells.
Amplifications of the 12p13 chromosomal band, comprising the FoxM1 gene, have been reported in numerous tumors such as cervical squamous cell carcinomas, breast adenocarcinomas, nasopharyngeal carcinomas and head and neck squamous cell carcinomas.
Entity name
FoxM1 expression is affected (low) in cells from patients with progeria and FoxM1-deficient cells senesce prematurely. Inversely, increased levels of FoxM1B in regenerating liver of old transgenic mice elevate hepatocyte proliferation to levels similar to those observed in young regenerating mouse liver.


Pubmed IDLast YearTitleAuthors
164522312006Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice.Kalin TV et al
150825322004Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor.Kalinichenko VV et al
164890162006The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer.Kim IM et al
94417471997The human TRIDENT/HFH-11/FKHL16 gene: structure, localization, and promoter characterization.Korver W et al
146470662003Growth hormone stimulates proliferation of old-aged regenerating liver through forkhead box m1b.Krupczak-Hollis K et al
105238411999Interaction of the fork head domain transcription factor MPP2 with the human papilloma virus 16 E7 protein: enhancement of transformation and transactivation.Lüscher-Firzlaff JM et al
170149652007FoxM1: at the crossroads of ageing and cancer.Laoukili J et al
165851842006FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells.Liu M et al
107419682000Mitotic misregulation and human aging.Ly DH et al
156710632005Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c.Ma RY et al
150240562004Forkhead box M1B transcriptional activity requires binding of Cdk-cyclin complexes for phosphorylation-dependent recruitment of p300/CBP coactivators.Major ML et al
178911722008An N-terminal inhibitory domain modulates activity of FoxM1 during cell cycle.Park HJ et al
157208002004Identification and validation of commonly overexpressed genes in solid tumors by comparison of microarray data.Pilarsky C et al
157216352005Conventional and array-based comparative genomic hybridization analysis of nasopharyngeal carcinomas from the Mediterranean area.Rodriguez S et al
171017822007Chk2 mediates stabilization of the FoxM1 transcription factor to stimulate expression of DNA repair genes.Tan Y et al
121834372002FOXM1 is a downstream target of Gli1 in basal cell carcinomas.Teh MT et al
163145122005Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase.Wang IC et al
122210982002Increased hepatic Forkhead Box M1B (FoxM1B) levels in old-aged mice stimulated liver regeneration through diminished p27Kip1 protein levels and increased Cdc25B expression.Wang X et al
115729932001Increased levels of forkhead box M1B transcription factor in transgenic mouse hepatocytes prevent age-related proliferation defects in regenerating liver.Wang X et al
178047442007Down-regulation of Forkhead Box M1 transcription factor leads to the inhibition of invasion and angiogenesis of pancreatic cancer cells.Wang Z et al
180209432007FOXM1, a typical proliferation-associated transcription factor.Wierstra I et al
90322901997Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues.Ye H et al

Other Information

Locus ID:

NCBI: 2305
MIM: 602341
HGNC: 3818
Ensembl: ENSG00000111206


dbSNP: 2305
ClinVar: 2305
TCGA: ENSG00000111206


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic G2-G2/M phasesREACTOMER-HSA-453274
G2/M TransitionREACTOMER-HSA-69275
Cyclin A/B1 associated events during G2/M transitionREACTOMER-HSA-69273
Polo-like kinase mediated eventsREACTOMER-HSA-156711

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
163145122005Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase.263
283440402017m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program.233
220145702011FoxM1 promotes β-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis.211
205314062010A human B-cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers.155
219788252012FOXM1: From cancer initiation to progression and treatment.152
170149652007FoxM1: at the crossroads of ageing and cancer.150
159585622005Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe.145
164890162006The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer.140
191604882008Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression.138
165851842006FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells.136


Jamila Laoukili ; Monica Alvarez Fernandez ; René H Medema

FOXM1 (forkhead box M1)

Atlas Genet Cytogenet Oncol Haematol. 2008-02-01

Online version: