EHF (ets homologous factor)

2012-04-01   Giuseppina M Carbone , Carlo V Catapano , Domenico Albino 

Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland (IOSI), Via Vela 6, Bellinzona, 6500 Switzerland

Identity

HGNC
LOCATION
11p13
IMAGE
Atlas Image
LOCUSID
ALIAS
ESE3,ESE3B,ESEJ
FUSION GENES

DNA/RNA

Note

Tumor suppressor gene.
Atlas Image
Schematic diagram of the EHF gene comprising 9 exons (in red). The sizes in base pairs (bp) of exons (below) are shown.

Description

DNA Size: 39,72 Kb, 9 exons.

Transcription

See above figure B.

Proteins

Atlas Image

Description

As reported by Kas et al., (J Biol Chem. 2000) sequence analysis revealed an open reading frame of 277 amino acids and a predicted molecular mass of 32,3 kDa for ESE-3a and an open reading frame encoding a 300-amino acid protein with a predicted molecular mass of 34,9 kDa for ESE-3b. In addition, several potential phosphorylation sites are present in ESE-3b including two potential protein kinase C phosphorylation sites, three casein kinase II phosphorylation sites, and one potential JNK/p38/ ERK kinase phosphorylation sites ((S/T)P) in the central region of ESE-3, just behind the alternatively spliced exon.
Atlas Image
Schematic representation of the two ESE3 protein isoforms. The pointed domain (PNT) and the Ets binding site (Ets DNA binding) domain are shown. PNT: (Pointed domain); EBS: (Ets binding site).

Expression

Normal epithelium.

Localisation

Nuclear.

Function

Transcription factor that binds to DNA sequences containing the ETS factor consensus nucleotide core sequence GGAA. May act as a repressor for a specific subset of ETS/AP-1-responsive genes and as a modulator of the nuclear response to RAS and mitogen-activated protein kinase (MAPK) signaling cascades. Involved in negative regulation of the expression of EZH2 through ETS binding sequences on the EZH2 promoter in normal prostate epithelial cells, prostate cancer cells and prostate tumors. Involved in positive regulation of NKX3.1 in normal prostate epithelial cells through ETS binding site in the gene promoter. Involved in the regulation of the expression of caspase-3 through ETS binding sequences on the caspase-3 promoter in prostate cancer cells. Involved in regulation of TNFRSF10B/DR5 expression through ETS binding sequences on the TNFRSF10B/DR5 promoter. May play a role in regulating epithelial cell differentiation and contribute to development and tumorigenesis by acting as a tumor suppressor gene.

Mutations

Note

Unknown.

Germinal

Unknown.

Somatic

Unknown.

Implicated in

Entity name
Human malignancies
Note
Albino et al. (Cancer Research, 2012) showed that ESE3, an endogenously expressed ETS transcription factor, controls prostate epithelial cell differentiation and stem-like potential. Stable ESE3 knockdown in prostate epithelial cells induced epithelial-to-mesenchymal transition (EMT), stem-like features, tumour-initiating and metastatic properties. Conversely, re-expression of ESE3 in prostate cancer cells reduced stem-like and tumorigenic potential. Mechanistically, ESE3/EHF maintains in a repressive state key EMT and Cancer stem cells (CSC) genes, including TWIST1, ZEB2, BMI1 and POU5F1, by directly binding to novel ETS binding sites identified in their promoters. Analysis of human tissue microarrays showed that reduced ESE3 expression was an early event and frequently independent of other ETS gene alterations. Analyses of multiple microarray datasets linked loss of ESE3/EHF expression to a distinct group of prostate tumors. ESE3 low tumors displayed distinctive molecular and biological characteristics, including increased expression of EMT and CSC genes and close similarity to ESE3 knockdown prostate epithelial cells. Low ESE3 expression was associated with increased biochemical recurrence and reduced overall survival after prostatectomy.
Entity name
Prostate cancer
Note
The ESE3 expression is reduced in prostate tumors.
Disease
Prostate cancer (possibly implicated in other solid tumors of epithelial origin).
Oncogenesis
Cangemi et al. (Oncogene 2008) and Albino et al. (Cancer Research, 2012) propose a tumor suppressor role in prostate cancer for ESE3. Albino et al. (Cancer Research, 2012) propose the possibility to identify molecularly defined tumour subgroups based on the exclusive loss of ESE3 expression level.

Bibliography

Pubmed IDLast YearTitleAuthors
225056492012ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features.Albino D et al
163804522006Epithelial-specific transcription factor ESE-3 is involved in the development of monocyte-derived DCs.Appel S et al
180379582008Reduced expression and tumor suppressor function of the ETS transcription factor ESE-3 in prostate cancer.Cangemi R et al
106447702000ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1.Kas K et al
105278511999Human chromosomal localization, tissue/tumor expression, and regulatory function of the ets family gene EHF.Kleinbaum LA et al
204799322010ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer.Kunderfranco P et al
170276472006ESE-3 transcription factor is involved in the expression of death receptor (DR)-5 through putative Ets sites.Lim JH et al
124440292002Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung.Silverman ES et al
165548112006Human chromosome 11 DNA sequence and analysis including novel gene identification.Taylor TD et al
112594072001The epithelium-specific ETS protein EHF/ESE-3 is a context-dependent transcriptional repressor downstream of MAPK signaling cascades.Tugores A et al

Other Information

Locus ID:

NCBI: 26298
MIM: 605439
HGNC: 3246
Ensembl: ENSG00000135373

Variants:

dbSNP: 26298
ClinVar: 26298
TCGA: ENSG00000135373
COSMIC: EHF

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000135373ENST00000257831Q9NZC4
ENSG00000135373ENST00000450654Q9NZC4
ENSG00000135373ENST00000525253E9PQR6
ENSG00000135373ENST00000527935E9PPS9
ENSG00000135373ENST00000529527E9PN75
ENSG00000135373ENST00000530286Q9NZC4
ENSG00000135373ENST00000531728E9PPS9
ENSG00000135373ENST00000531794Q9NZC4
ENSG00000135373ENST00000532302E9PQX0
ENSG00000135373ENST00000533754Q9NZC4

Expression (GTEx)

0
50
100
150
200

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
225056492012ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features.45
184752892008Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation.29
180379582008Reduced expression and tumor suppressor function of the ETS transcription factor ESE-3 in prostate cancer.28
124440292002Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung.20
271971752016Activation of the Lin28/let-7 Axis by Loss of ESE3/EHF Promotes a Tumorigenic and Stem-like Phenotype in Prostate Cancer.20
284613362017Ets homologous factor (EHF) has critical roles in epithelial dysfunction in airway disease.18
216177032011A member of the ETS family, EHF, and the ATPase RUVBL1 inhibit p53-mediated apoptosis.15
277329362016The ETS factor ESE3/EHF represses IL-6 preventing STAT3 activation and expansion of the prostate cancer stem-like compartment.12
277875202016Increased expression of EHF via gene amplification contributes to the activation of HER family signaling and associates with poor survival in gastric cancer.12
241053692014The CF-modifying gene EHF promotes p.Phe508del-CFTR residual function by altering protein glycosylation and trafficking in epithelial cells.11

Citation

Giuseppina M Carbone ; Carlo V Catapano ; Domenico Albino

EHF (ets homologous factor)

Atlas Genet Cytogenet Oncol Haematol. 2012-04-01

Online version: http://atlasgeneticsoncology.org/gene/40421/ehf-(ets-homologous-factor)