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FLASH GENE
Symbol FOXM1 contributors: mct/pgu - updated : 16-09-2018
HGNC name forkhead box M1
HGNC id 3818
Location 12p13.33      Physical location : 2.966.849 - 2.986.303
Synonym name
  • M-phase phosphoprotein 2
  • forkhead (Drosophila)-like 16
  • trident
  • transcription factor-like 16
  • HNF-3/fork-head homolog 11
  • hepatocyte nuclear factor 3 forkhead homolog 11
  • winged-helix factor from INS-1 cells
    • Synonym symbol(s) HNF3, FKHL16, FOXM1B, HFH-11, HFH11, HNF-3, INS-1, MPHOSPH2, MPP-2, MPP2, PIG29, TGT3, WIN, MPP2, PIG29, TRIDENT
    DNA
    TYPE functioning gene
    STRUCTURE 19.47 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text at least three classes of transcripts
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3641 - 801 - 2007 18020943
  • isoform 1
    • 9 - 3527 - 763 - 2007 18020943
  • cyclin/Cdk-binding LXL-motif is required for its interaction with CDK2, CDC2, and CDKN1B
  • activated by cyclin B/Cdk (cyclin-dependent kinase) 1
  • FOXM1b, HFH-11B, isoform 2
    • 8 - 3487 - 748 - 2007 18020943
  • interacts with the coactivator and histone acetyltransferase PCAF
  • transactivates the c-myc promoter by binding directly to its TATA-boxes
  • FOXM1c, isoform 3
  • predominantly overexpressed in oesophageal squamous cell carcinoma (ESCC) cell lines
  • CCND1/CDK4 increases the transcriptional activity of FOXM1c without phosphorylating FOXM1c
    • 8 - 3506 - 748 - 2007 18020943
    8 - 3503 - 747 - 2007 18020943
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
    Endocrineneuroendocrinepituitary  highly
    Lymphoid/Immunethymus    
    Reproductivefemale systemovary  highly
     female systemuteruscervix highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatid
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    cell cycle     cell cycle, M
    Text mesenchymal epithelial cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a forkhead (FH, winged helix) domain
  • two loops-wings on the C terminal side of helix-turn-helix domain
  • a cyclin/Cdk-binding LXL-motif
    • HOMOLOGY
    interspecies homolog to murine Trident
    homolog to Drosophila homeo forkhead DNA binding domain
    Homologene
    FAMILY
  • HNF-3, FKH family of transcriptional activators
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • important positive regulator of DNA replication and mitosis in a variety of cell types
  • proliferation-associated transcription factor, stimulating proliferation by promoting both G1/S- and G2/M-transition and implicated in tumorigenesis
  • embryonic transcriptional regulator, involved in cell proliferation
  • critical for surfactant homeostasis and lung maturation before birth and is required for adaptation to air breathing
  • has critical functions in tumor development and progression
  • regulate, variously, proliferation and/or spindle formation during the G2/M transition of the cell cycle
  • functions in SHH-induced neuroproliferation are restricted to the regulation of the G2/M transition in cerebellar granule neuron precursors, most probably through transcriptional effects on target genes such as those coding for B-type cyclins
  • a typical proliferation-associated transcription factor that stimulates proliferation by promoting S-phase entry as well as M-phase entry and is involved in proper execution of mitosis
  • regulates genes that control G1/S-transition, S-phase progression, G2/M-transition and M-phase progression
  • having two different transactivation mechanisms, the regulation of its transcriptional activity by proliferation versus anti-proliferation signals and its function in normal cell cycle progression and tumorigenesis
  • key regulator of oxidative stress that contributes to malignant transformation and tumor cell survival
  • transcriptionally active during a DNA-damage-induced G2 arrest and is essential for checkpoint recovery
  • critical involvement in maintenance of stem cell pluripotency
  • in cancer cells the interaction between FOXM1 and NPM1 is necessary for sustaining the level and localization of FOXM1 and it may be required for cancer progression
  • expression of FOXM1 in macrophages is required for pulmonary inflammation, recruitment of macrophages into tumor sites and lung tumor growth
  • is required for KRAS signaling in distal lung epithelium and provides a mechanism integrating Kras and canonical WNT/CTNNB1 signaling during lung development
  • is required for differentiation and maintenance of epithelial cells lining conducting airways.
  • regulates genes critical for allergen-induced lung inflammation and goblet cell metaplasia
  • is a critical regulator of the G1/S and G2/M cell cycle transitions, as well as of the mitotic spindle assembly
  • FOXM1 controls the cell cycle through its association with CDC25A
  • is required for lung fibrosis and epithelial-to-mesenchymal transition
  • promoted EMT in breast cancer cells by stimulating the transcription of EMT-related genes such as SNAI2
  • strongly activates promoters of G2/M phase genes and weakly activates those induced in S phase
  • is an essential effector of G2/M-phase transition, mitosis and the DNA damage response
  • function for FOXM1 in interkinetic nuclear migration in the developing telencephalon and anxiety-related behavior
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • FOXM1-LDHA signaling functioned as a stimulator of glycolysis and promoted Gastric cancer progression
    • a component
    INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • direct transcriptional activator of SFTPA, SFTPB
  • AKT1 and FOXM1 are downstream targets of NOTCH1 signaling
  • NPM1 interacts with FOXM1 and their interaction is required for sustaining the level and localization of FOXM1
  • MYBL2 is required as a pioneer factor to enable FOXM1 binding to G2/M gene promoters
  • FOXM1 transcription factor is a key downstream target of activated KRAS(G12D)
  • FOXM1 directly bound to and increased transcriptional activity of the AXIN2 promoter region
  • its downregulation is required for contact inhibition by regulating expression of cyclin A and polo-like kinase 1
  • binds and regulates a group of genes which are mainly involved in controlling late cell cycle events in the G(2) and M phases
  • FOXM1 directly regulates CDC25A gene transcription via direct promoter binding and indirect activation of E2F-dependent pathways
  • endogenously bind to and stimulate the promoter of SNAI2 that is crucial for EMT progression
  • bound to cell cycle-regulated genes with peak expression in both S phase and G2/M phases
  • KLF1 binds to the FOXM1 gene promoter in blood cells
  • is a direct target gene of MEIS2 and is required for MEIS2 to upregulate mitotic genes
  • IRF1 is a transcriptional target of FOXM1c and a FOXM1c-binding site is in the IRF1 promoter region
  • partnering role of EPS8 with FOXM1 in the regulation of cancer cell proliferation
  • MELK enhances tumorigenesis, migration, invasion and metastasis of Esophageal squamous cell carcinoma (ESCC) cells via activation of FOXM1 signaling pathway
    • cell & other
    REGULATION
    activated by Cdk activity which is required for activation of FOXM1
    induced by RAS, requiring reactive oxygene species
    inhibited by DACH1 (DACH1 displaced FOXM1 from the known target gene promoters including CDC25B, Survivin, CENPA, and CENPB)
    repressed by TP53
    Other reactivated in proliferating epithelial and mesenchymal cells by proliferative signals or oxidative stress
    is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites, and SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    from respiratory epithelium did not influence branching lung morphogenesis or epithelial proliferation, but impaired lung sacculation, delayed type I cell differentiation, and reduced expression of surfactant-associated proteins, causing respiratory failure after birth
    tumoral     --over  
    overexpressed in OCSCC
    tumoral     --over  
    overexpression of FOXM1, XIAP, and BIRC5 contributes to the development of drug-resistance and is associated with poor clinical outcome in breast cancer patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    respiratorylung 
    provide novel strategies for diagnosis, prevention, and treatment of respiratory distress syndrome in preterm infants
    cancerhemopathy 
    curcumin together with FOXM1 targeting agents may be effective for acute myeloid leukemia therapy
    cancer  
    targeting FOXM1 increases apoptosis and inhibits tumor growth
    ANIMAL & CELL MODELS