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FOXM1 (forkhead box M1)

Identity

Other namesFKHL16
FOXM1B
HFH-11
HFH11
HNF-3
INS-1
MPHOSPH2
MPP-2
MPP2
PIG29
TGT3
TRIDENT
HGNC (Hugo) FOXM1
LocusID (NCBI) 2305
Location 12p13.33
Location_base_pair Starts at 2966847 and ends at 2986321 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
Description The gene spans 25 kb and contains 10 exons.
Transcription 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.

Protein

 
  hFoxM1C
Description 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.
Expression 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.
Localisation 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.
Function FoxM1 acts as a transcriptional activator of the G2-M-specific gene cluster in mammalian cells.
Homology Homology with other Forkhead transcription factors in the FKH DNA Binding Domain.

Implicated in

Entity Cancer
Disease 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.
Cytogenetics 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 Ageing
Disease 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.
  

External links

Nomenclature
HGNC (Hugo)FOXM1   3818
Cards
AtlasFOXM1ID40631ch12p13
Entrez_Gene (NCBI)FOXM1  2305  forkhead box M1
GeneCards (Weizmann)FOXM1
Ensembl (Hinxton)ENSG00000111206 [Gene_View]  chr12:2966847-2986321 [Contig_View]  FOXM1 [Vega]
ICGC DataPortalENSG00000111206
cBioPortalFOXM1
AceView (NCBI)FOXM1
Genatlas (Paris)FOXM1
WikiGenes2305
SOURCE (Princeton)NM_001243088 NM_001243089 NM_021953 NM_202002 NM_202003
Genomic and cartography
GoldenPath (UCSC)FOXM1  -  12p13.33   chr12:2966847-2986321 -  12p13   [Description]    (hg19-Feb_2009)
EnsemblFOXM1 - 12p13 [CytoView]
Mapping of homologs : NCBIFOXM1 [Mapview]
OMIM602341   
Gene and transcription
Genbank (Entrez)AK291206 AK313845 AW780338 AY542306 BC006192
RefSeq transcript (Entrez)NM_001243088 NM_001243089 NM_021953 NM_202002 NM_202003
RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NG_029590 NT_009759 NW_001838049 NW_004929382
Consensus coding sequences : CCDS (NCBI)FOXM1
Cluster EST : UnigeneHs.735243 [ NCBI ]
CGAP (NCI)Hs.735243
Alternative Splicing : Fast-db (Paris)GSHG0007179
Alternative Splicing GalleryENSG00000111206
Gene ExpressionFOXM1 [ NCBI-GEO ]     FOXM1 [ SEEK ]   FOXM1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ08050 (Uniprot)
NextProtQ08050  [Medical]
With graphics : InterProQ08050
Splice isoforms : SwissVarQ08050 (Swissvar)
Domaine pattern : Prosite (Expaxy)FORK_HEAD_1 (PS00657)    FORK_HEAD_2 (PS00658)    FORK_HEAD_3 (PS50039)   
Domains : Interpro (EBI)TF_fork_head [organisation]   TF_fork_head_CS [organisation]   WHTH_DNA-bd_dom [organisation]  
Related proteins : CluSTrQ08050
Domain families : Pfam (Sanger)Fork_head (PF00250)   
Domain families : Pfam (NCBI)pfam00250   
Domain families : Smart (EMBL)FH (SM00339)  
DMDM Disease mutations2305
Blocks (Seattle)Q08050
PDB (SRS)3G73   
PDB (PDBSum)3G73   
PDB (IMB)3G73   
PDB (RSDB)3G73   
Human Protein AtlasENSG00000111206 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ08050
HPRD03823
IPIIPI00032162   IPI00216686   IPI00401044   IPI01009236   IPI01009714   
Protein Interaction databases
DIP (DOE-UCLA)Q08050
IntAct (EBI)Q08050
FunCoupENSG00000111206
BioGRIDFOXM1
InParanoidQ08050
Interologous Interaction database Q08050
IntegromeDBFOXM1
STRING (EMBL)FOXM1
Ontologies - Pathways
Ontology : AmiGOG2/M transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  negative regulation of transcription from RNA polymerase II promoter  mitotic cell cycle  regulation of cell growth  vasculogenesis  liver development  DNA binding  DNA binding  sequence-specific DNA binding transcription factor activity  sequence-specific DNA binding transcription factor activity  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  nucleoplasm  nucleolus  cytoplasm  DNA repair  regulation of transcription, DNA-templated  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  transcription from RNA polymerase II promoter  DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator  cell cycle  positive regulation of cell proliferation  protein kinase binding  negative regulation of stress-activated MAPK cascade  regulation of cell proliferation  sequence-specific DNA binding  transcription regulatory region DNA binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  regulation of Ras protein signal transduction  regulation of cell cycle  regulation of cell cycle arrest  negative regulation of cell aging  regulation of reactive oxygen species metabolic process  positive regulation of double-strand break repair  
Ontology : EGO-EBIG2/M transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  negative regulation of transcription from RNA polymerase II promoter  mitotic cell cycle  regulation of cell growth  vasculogenesis  liver development  DNA binding  DNA binding  sequence-specific DNA binding transcription factor activity  sequence-specific DNA binding transcription factor activity  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  nucleoplasm  nucleolus  cytoplasm  DNA repair  regulation of transcription, DNA-templated  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  transcription from RNA polymerase II promoter  DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator  cell cycle  positive regulation of cell proliferation  protein kinase binding  negative regulation of stress-activated MAPK cascade  regulation of cell proliferation  sequence-specific DNA binding  transcription regulatory region DNA binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  regulation of Ras protein signal transduction  regulation of cell cycle  regulation of cell cycle arrest  negative regulation of cell aging  regulation of reactive oxygen species metabolic process  positive regulation of double-strand break repair  
Protein Interaction DatabaseFOXM1
Wikipedia pathwaysFOXM1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)FOXM1
snp3D : Map Gene to Disease2305
SNP (GeneSNP Utah)FOXM1
SNP : HGBaseFOXM1
Genetic variants : HAPMAPFOXM1
Exome VariantFOXM1
1000_GenomesFOXM1 
ICGC programENSG00000111206 
Somatic Mutations in Cancer : COSMICFOXM1 
CONAN: Copy Number AnalysisFOXM1 
Mutations and Diseases : HGMDFOXM1
Genomic VariantsFOXM1  FOXM1 [DGVbeta]
dbVarFOXM1
ClinVarFOXM1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM602341   
MedgenFOXM1
GENETestsFOXM1
Disease Genetic AssociationFOXM1
Huge Navigator FOXM1 [HugePedia]  FOXM1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneFOXM1
Homology/Alignments : Family Browser (UCSC)FOXM1
Phylogenetic Trees/Animal Genes : TreeFamFOXM1
Chemical/Protein Interactions : CTD2305
Chemical/Pharm GKB GenePA28236
Clinical trialFOXM1
Cancer Resource (Charite)ENSG00000111206
Other databases
Probes
Litterature
PubMed178 Pubmed reference(s) in Entrez
CoreMineFOXM1
iHOPFOXM1
OncoSearchFOXM1

Bibliography

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FoxM1 is required for execution of the mitotic programme and chromosome stability.
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Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c.
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REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written02-2008Jamila 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)

Citation

This paper should be referenced as such :
Laoukili, J ; Alvarez, Fernandez M ; Medema, RH
FOXM1 (forkhead box M1)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(6):432-434.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/FOXM1ID40631ch12p13.html

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indexed on : Fri Aug 8 11:03:43 CEST 2014

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