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POU1F1 (POU class 1 homeobox 1)

Written2014-02Jean-Louis Franc, Denis Becquet, Anne-Marie François-Bellan
CRN2M, UMR7286 Aix-Marseille Universite, CNRS, Faculte de Medecine, Bd P. Dramard, Marseille, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPIT1
POU domain class 1
Alias_symbol (synonym)GHF-1
POU1F1a
Other aliasCPHD1
Pit-1
HGNC (Hugo) POU1F1
LocusID (NCBI) 5449
Atlas_Id 46362
Location 3p11.2  [Link to chromosome band 3p11]
Location_base_pair Starts at 87259633 and ends at 87276587 bp from pter ( according to hg19-Feb_2009)  [Mapping POU1F1.png]
Fusion genes
(updated 2016)
NUP98 (11p15.4) / POU1F1 (3p11.2)POU1F1 (3p11.2) / TMPRSS15 (21q21.1)

DNA/RNA

Note The anterior pituitary-specific transcription factor POU1F1 was initially identified and cloned as a transactivator of prolactin (PRL), growth hormone (GH), and TSHβ-subunit genes (Bodner et al., 1988; Ingraham et al., 1988). Transcription produces 2 alternatively spliced mRNAs α (NM_000306.2) and β (NM_001122757.1).
 
  Structure of POU1F1 gene and its transcripts encoded on minus strand of chromosome 3.
Description The human POU1F1 gene is composed of 6 exons (Theill et al., 1992).
Transcription Two transcripts have been reported for this gene.

Protein

 
Description The main protein isoform expressed in pituitary cells is POU1F1α. This isoform, also named PIT-1.b or PIT-1α, has 291 aa. The predicted protein corresponding to POU1F1β, also named PIT-1.a or PIT-1β, has 317 aa and acts as a repressor in pituitary cells (Theill et al., 1992; Jonsen et al., 2009). POU1F1 is structurally related to the POU family of transcriptional regulators, containing a characteristic POU domain divided into two regions, the POU-specific and homeo subdomains. The POUs-specific domain consists of 75 amino acids, comprises 4 α-helices, and contributes to the DNA binding specificity and protein / protein interactions (Ingraham et al., 1990; Jacobson et al., 1997). The homeodomain is composed of 60 amino and contains 3 α-helices. The N-terminal part of POU1F1 is involved in the transcriptional activity. POU1F1 binds as a dimer to most DNA response elements (for review see Phillips and Luisi, 2000).
Expression The expression of POU1F1 is largely restricted in the pituitary gland in somato- thyreo- and lacto-trope cells, but this factor is also expressed in some extrapituitary tissues and cell lines, including the mammary gland (Gil-Puig et al., 2002).
Localisation The localization of POU1F1 is nuclear.
Function POU1F1 is a member of the POU family of transcription factors. This factor is required for terminal differentiation of the somatotrope, lactotrope and thyrotrope cell types (Ingraham et al., 1988; Cohen et al., 1996). This factor is also implicated in the cell growth and prevents the apoptotic cell death (Pellegrini et al., 2006).

Mutations

Note In humans, mutation in the POU1F1 gene has been shown to be responsible for combined pituitary hormone deficiency (for review see Quentien et al., 2006) (see below).

Implicated in

Note
  
Entity Pituitary adenoma
Prognosis POU1F1 is overexpressed in GH, PRL and TSH pituitary adenomas (Asa et al., 1993; Delhase et al., 1993; Pellegrini et al., 1994) and the increased expression in adenomas is compatible with the role of POU1F1 in cell proliferation. Interestingly, human non-functioning pituitary adenomas also express POU1F1, especially it was expressed in all alpha SU positive nonfunctioning adenomas (Osamura et al., 1999).
  
  
Entity Combined pituitary hormone deficiency (CPHD)
Prognosis In humans, mutation in the POU1F1 gene has been shown to be responsible for combined pituitary hormone deficiency. This syndrome is a disease characterized by the lack of PRL, GH, and TSHbeta produced by the somato- lacto- and thyreo-tropes cells. At least sixteen distinct recessive or dominant POU1F1 mutations have been described to date (Cushman et al., 2002; Dattani, 2005). The molecular mechanisms underlying their effects can be dominant inhibition of transcription or inability to bind to DNA. The R271W mutation is the most commonly occurring POU1F1 gene defect (Radovick et al., 1992). Other mutations, such as F135C, show a decreased transactivation activity although the DNA binding property is conserved (Vallette-Kasic et al., 2001).
 
Location of the Pit-1 gene mutation.
  
  
Entity Breast carcinoma
Prognosis POU1F1 was expressed in normal human breast tissue but its mRNA expression levels is significantly higher in breast adenocarcinoma. This deregulation promotes tumor growth and metastasis (Gil-Puig et al., 2005; Ben-Batalla et al., 2010).
  
  
Entity Acute myeloid leukemia
Prognosis In acute myeloid leukemia POU1F1 has been identified as a new fusion partner of NUP98 gene (Lisboa et al., 2013).
  
  

Bibliography

Cell type-specific expression of the pituitary transcription activator pit-1 in the human pituitary and pituitary adenomas.
Asa SL, Puy LA, Lew AM, Sundmark VC, Elsholtz HP.
J Clin Endocrinol Metab. 1993 Nov;77(5):1275-80.
PMID 8077321
 
Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis.
Ben-Batalla I, Seoane S, Garcia-Caballero T, Gallego R, Macia M, Gonzalez LO, Vizoso F, Perez-Fernandez R.
J Clin Invest. 2010 Dec;120(12):4289-302. doi: 10.1172/JCI42015. Epub 2010 Nov 8.
PMID 21060149
 
The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein.
Bodner M, Castrillo JL, Theill LE, Deerinck T, Ellisman M, Karin M.
Cell. 1988 Nov 4;55(3):505-18.
PMID 2902927
 
Role of Pit-1 in the gene expression of growth hormone, prolactin, and thyrotropin.
Cohen LE, Wondisford FE, Radovick S.
Endocrinol Metab Clin North Am. 1996 Sep;25(3):523-40. (REVIEW)
PMID 8879985
 
Genetic defects in the development and function of the anterior pituitary gland.
Cushman LJ, Showalter AD, Rhodes SJ.
Ann Med. 2002;34(3):179-91. (REVIEW)
PMID 12173688
 
Growth hormone deficiency and combined pituitary hormone deficiency: does the genotype matter?
Dattani MT.
Clin Endocrinol (Oxf). 2005 Aug;63(2):121-30. (REVIEW)
PMID 16060904
 
Pit-1/GHF-1 expression in pituitary adenomas: further analogy between human adenomas and rat SMtTW tumours.
Delhase M, Vergani P, Malur A, Velkeniers B, Teugels E, Trouillas J, Hooghe-Peters EL.
J Mol Endocrinol. 1993 Oct;11(2):129-39.
PMID 8297469
 
Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation.
Gil-Puig C, Seoane S, Blanco M, Macia M, Garcia-Caballero T, Segura C, Perez-Fernandez R.
Eur J Endocrinol. 2005 Aug;153(2):335-44.
PMID 16061841
 
The POU-specific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions.
Ingraham HA, Flynn SE, Voss JW, Albert VR, Kapiloff MS, Wilson L, Rosenfeld MG.
Cell. 1990 Jun 15;61(6):1021-33.
PMID 2350782
 
Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.
Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK.
Genes Dev. 1997 Jan 15;11(2):198-212.
PMID 9009203
 
The 26-amino acid beta-motif of the Pit-1beta transcription factor is a dominant and independent repressor domain.
Jonsen MD, Duval DL, Gutierrez-Hartmann A.
Mol Endocrinol. 2009 Sep;23(9):1371-84. doi: 10.1210/me.2008-0137. Epub 2009 Jun 25.
PMID 19556346
 
POU1F1 is a novel fusion partner of NUP98 in acute myeloid leukemia with t(3;11)(p11;p15).
Lisboa S, Cerveira N, Bizarro S, Correia C, Vieira J, Torres L, Mariz JM, Teixeira MR.
Mol Cancer. 2013 Jan 18;12:5. doi: 10.1186/1476-4598-12-5.
PMID 23332017
 
Pit-1 positive alpha-subunit positive nonfunctioning human pituitary adenomas: a dedifferentiated GH cell lineage?
Osamura RY, Tahara S, Komatsubara K, Itoh Y, Kajiwara H, Kurotani R, Sanno N, Teramoto A.
Pituitary. 1999 May;1(3-4):269-71. (REVIEW)
PMID 11081207
 
Involvement of the pituitary-specific transcription factor pit-1 in somatolactotrope cell growth and death: an approach using dominant-negative pit-1 mutants.
Pellegrini I, Roche C, Quentien MH, Ferrand M, Gunz G, Thirion S, Bagnis C, Enjalbert A, Franc JL.
Mol Endocrinol. 2006 Dec;20(12):3212-27. Epub 2006 Aug 10.
PMID 16901973
 
The virtuoso of versatility: POU proteins that flex to fit.
Phillips K, Luisi B.
J Mol Biol. 2000 Oct 6;302(5):1023-39. (REVIEW)
PMID 11183772
 
Pituitary transcription factors: from congenital deficiencies to gene therapy.
Quentien MH, Barlier A, Franc JL, Pellegrini I, Brue T, Enjalbert A.
J Neuroendocrinol. 2006 Sep;18(9):633-42. (REVIEW)
PMID 16879162
 
A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency.
Radovick S, Nations M, Du Y, Berg LA, Weintraub BD, Wondisford FE.
Science. 1992 Aug 21;257(5073):1115-8.
PMID 1509262
 
Differential splicing of the GHF1 primary transcript gives rise to two functionally distinct homeodomain proteins.
Theill LE, Hattori K, Lazzaro D, Castrillo JL, Karin M.
EMBO J. 1992 Jun;11(6):2261-9.
PMID 1600947
 
Combined pituitary hormone deficiency due to the F135C human Pit-1 (pituitary-specific factor 1) gene mutation: functional and structural correlates.
Vallette-Kasic S, Pellegrini-Bouiller I, Sampieri F, Gunz G, Diaz A, Radovick S, Enjalbert A, Brue T.
Mol Endocrinol. 2001 Mar;15(3):411-20.
PMID 11222742
 

Citation

This paper should be referenced as such :
JL Franc, D Becquet, AM Franè_ois-Bellan
POU1F1 (POU class 1 homeobox 1)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(10):728-730.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/POU1F1ID46362ch3p11.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Lung: Translocations in Squamous Cell Carcinoma


External links

Nomenclature
HGNC (Hugo)POU1F1   9210
Cards
AtlasPOU1F1ID46362ch3p11
Entrez_Gene (NCBI)POU1F1  5449  POU class 1 homeobox 1
AliasesCPHD1; GHF-1; PIT1; POU1F1a; 
Pit-1
GeneCards (Weizmann)POU1F1
Ensembl hg19 (Hinxton)ENSG00000064835 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000064835 [Gene_View]  chr3:87259633-87276587 [Contig_View]  POU1F1 [Vega]
ICGC DataPortalENSG00000064835
TCGA cBioPortalPOU1F1
AceView (NCBI)POU1F1
Genatlas (Paris)POU1F1
WikiGenes5449
SOURCE (Princeton)POU1F1
Genetics Home Reference (NIH)POU1F1
Genomic and cartography
GoldenPath hg38 (UCSC)POU1F1  -     chr3:87259633-87276587 -  3p11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)POU1F1  -     3p11.2   [Description]    (hg19-Feb_2009)
EnsemblPOU1F1 - 3p11.2 [CytoView hg19]  POU1F1 - 3p11.2 [CytoView hg38]
Mapping of homologs : NCBIPOU1F1 [Mapview hg19]  POU1F1 [Mapview hg38]
OMIM173110   613038   
Gene and transcription
Genbank (Entrez)BC152851 D10216 L18781 S73501 X62429
RefSeq transcript (Entrez)NM_000306 NM_001122757
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)POU1F1
Cluster EST : UnigeneHs.591654 [ NCBI ]
CGAP (NCI)Hs.591654
Alternative Splicing GalleryENSG00000064835
Gene ExpressionPOU1F1 [ NCBI-GEO ]   POU1F1 [ EBI - ARRAY_EXPRESS ]   POU1F1 [ SEEK ]   POU1F1 [ MEM ]
Gene Expression Viewer (FireBrowse)POU1F1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5449
GTEX Portal (Tissue expression)POU1F1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP28069   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP28069  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP28069
Splice isoforms : SwissVarP28069
PhosPhoSitePlusP28069
Domaine pattern : Prosite (Expaxy)HOMEOBOX_1 (PS00027)    HOMEOBOX_2 (PS50071)    POU_1 (PS00035)    POU_2 (PS00465)    POU_3 (PS51179)   
Domains : Interpro (EBI)Homeobox-like    Homeobox_CS    Homeobox_dom    Lambda_DNA-bd_dom    Pit_1    POU    POU_dom   
Domain families : Pfam (Sanger)Homeobox (PF00046)    Pou (PF00157)   
Domain families : Pfam (NCBI)pfam00046    pfam00157   
Domain families : Smart (EMBL)HOX (SM00389)  POU (SM00352)  
Conserved Domain (NCBI)POU1F1
DMDM Disease mutations5449
Blocks (Seattle)POU1F1
SuperfamilyP28069
Human Protein AtlasENSG00000064835
Peptide AtlasP28069
HPRD01409
IPIIPI00000794   IPI00216420   
Protein Interaction databases
DIP (DOE-UCLA)P28069
IntAct (EBI)P28069
FunCoupENSG00000064835
BioGRIDPOU1F1
STRING (EMBL)POU1F1
ZODIACPOU1F1
Ontologies - Pathways
QuickGOP28069
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  RNA polymerase II transcription factor binding  RNA polymerase II activating transcription factor binding  RNA polymerase II transcription coactivator activity  cell fate specification  chromatin binding  transcription factor activity, sequence-specific DNA binding  transcription corepressor activity  nucleus  transcription factor complex  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  positive regulation of cell proliferation  negative regulation of cell proliferation  determination of adult lifespan  B cell differentiation  positive regulation of inositol trisphosphate biosynthetic process  positive regulation of multicellular organism growth  regulation of insulin-like growth factor receptor signaling pathway  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  nuclear transport  somatotropin secreting cell development  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  RNA polymerase II transcription factor binding  RNA polymerase II activating transcription factor binding  RNA polymerase II transcription coactivator activity  cell fate specification  chromatin binding  transcription factor activity, sequence-specific DNA binding  transcription corepressor activity  nucleus  transcription factor complex  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  positive regulation of cell proliferation  negative regulation of cell proliferation  determination of adult lifespan  B cell differentiation  positive regulation of inositol trisphosphate biosynthetic process  positive regulation of multicellular organism growth  regulation of insulin-like growth factor receptor signaling pathway  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  nuclear transport  somatotropin secreting cell development  
NDEx NetworkPOU1F1
Atlas of Cancer Signalling NetworkPOU1F1
Wikipedia pathwaysPOU1F1
Orthology - Evolution
OrthoDB5449
GeneTree (enSembl)ENSG00000064835
Phylogenetic Trees/Animal Genes : TreeFamPOU1F1
HOVERGENP28069
HOGENOMP28069
Homologs : HomoloGenePOU1F1
Homology/Alignments : Family Browser (UCSC)POU1F1
Gene fusions - Rearrangements
Fusion : MitelmanNUP98/POU1F1 [11p15.4/3p11.2]  [t(3;11)(p11;p15)]  
Fusion : MitelmanPOU1F1/TMPRSS15 [3p11.2/21q21.1]  [t(3;21)(p11;q21)]  
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPOU1F1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)POU1F1
dbVarPOU1F1
ClinVarPOU1F1
1000_GenomesPOU1F1 
Exome Variant ServerPOU1F1
ExAC (Exome Aggregation Consortium)POU1F1 (select the gene name)
Genetic variants : HAPMAP5449
Genomic Variants (DGV)POU1F1 [DGVbeta]
DECIPHERPOU1F1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPOU1F1 
Mutations
ICGC Data PortalPOU1F1 
TCGA Data PortalPOU1F1 
Broad Tumor PortalPOU1F1
OASIS PortalPOU1F1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPOU1F1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPOU1F1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch POU1F1
DgiDB (Drug Gene Interaction Database)POU1F1
DoCM (Curated mutations)POU1F1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)POU1F1 (select a term)
intoGenPOU1F1
NCG5 (London)POU1F1
Cancer3DPOU1F1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM173110    613038   
Orphanet19033    19211    12618   
MedgenPOU1F1
Genetic Testing Registry POU1F1
NextProtP28069 [Medical]
TSGene5449
GENETestsPOU1F1
Target ValidationPOU1F1
Huge Navigator POU1F1 [HugePedia]
snp3D : Map Gene to Disease5449
BioCentury BCIQPOU1F1
ClinGenPOU1F1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5449
Chemical/Pharm GKB GenePA33534
Clinical trialPOU1F1
Miscellaneous
canSAR (ICR)POU1F1 (select the gene name)
Probes
Litterature
PubMed109 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePOU1F1
EVEXPOU1F1
GoPubMedPOU1F1
iHOPPOU1F1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Aug 1 17:34:22 CEST 2017

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