EHF (ets homologous factor)
2012-04-01 Giuseppina M Carbone , Carlo V Catapano , Domenico Albino AffiliationInstitute of Oncology Research (IOR), Oncology Institute of Southern Switzerland (IOSI), Via Vela 6, Bellinzona, 6500 Switzerland
Identity
HGNC
LOCATION
11p13
IMAGE
LOCUSID
ALIAS
ESE3,ESE3B,ESEJ
FUSION GENES
DNA/RNA
Note
Tumor suppressor gene.
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
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.
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 22505649 | 2012 | ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features. | Albino D et al |
| 16380452 | 2006 | Epithelial-specific transcription factor ESE-3 is involved in the development of monocyte-derived DCs. | Appel S et al |
| 18037958 | 2008 | Reduced expression and tumor suppressor function of the ETS transcription factor ESE-3 in prostate cancer. | Cangemi R et al |
| 10644770 | 2000 | ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1. | Kas K et al |
| 10527851 | 1999 | Human chromosomal localization, tissue/tumor expression, and regulatory function of the ets family gene EHF. | Kleinbaum LA et al |
| 20479932 | 2010 | ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer. | Kunderfranco P et al |
| 17027647 | 2006 | ESE-3 transcription factor is involved in the expression of death receptor (DR)-5 through putative Ets sites. | Lim JH et al |
| 12444029 | 2002 | Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung. | Silverman ES et al |
| 16554811 | 2006 | Human chromosome 11 DNA sequence and analysis including novel gene identification. | Taylor TD et al |
| 11259407 | 2001 | The 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
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38880187 | 2024 | ETS homologous factor, controlled by lysine-specific demethylase 5B, suppresses clear cell renal cell carcinoma by inducing Filamin-B. | 0 |
| 38880187 | 2024 | ETS homologous factor, controlled by lysine-specific demethylase 5B, suppresses clear cell renal cell carcinoma by inducing Filamin-B. | 0 |
| 33414441 | 2021 | Loss of EHF facilitates the development of treatment-induced neuroendocrine prostate cancer. | 9 |
| 33907840 | 2021 | EHF enhances malignancy by modulating AKT and MAPK/ERK signaling in non‑small cell lung cancer cells. | 2 |
| 34014591 | 2021 | Activation of EHF via STAT3 phosphorylation by LMP2A in Epstein-Barr virus-positive gastric cancer. | 13 |
| 34452885 | 2021 | Ese-3 Inhibits the Proliferation, Migration, and Invasion of HaCaT Cells by Downregulating PSIP1 and NUCKS1. | 3 |
| 34482266 | 2021 | Pancreatic cancer cell-derived microRNA-155-5p-containing extracellular vesicles promote immune evasion by triggering EHF-dependent activation of Akt/NF-κB signaling pathway. | 9 |
| 33414441 | 2021 | Loss of EHF facilitates the development of treatment-induced neuroendocrine prostate cancer. | 9 |
| 33907840 | 2021 | EHF enhances malignancy by modulating AKT and MAPK/ERK signaling in non‑small cell lung cancer cells. | 2 |
| 34014591 | 2021 | Activation of EHF via STAT3 phosphorylation by LMP2A in Epstein-Barr virus-positive gastric cancer. | 13 |
| 34452885 | 2021 | Ese-3 Inhibits the Proliferation, Migration, and Invasion of HaCaT Cells by Downregulating PSIP1 and NUCKS1. | 3 |
| 34482266 | 2021 | Pancreatic cancer cell-derived microRNA-155-5p-containing extracellular vesicles promote immune evasion by triggering EHF-dependent activation of Akt/NF-κB signaling pathway. | 9 |
| 32347431 | 2020 | Expression and prognostic significance of epithelial tissue-specific transcription factor ESE3 in hepatocellular carcinoma. | 3 |
| 32347431 | 2020 | Expression and prognostic significance of epithelial tissue-specific transcription factor ESE3 in hepatocellular carcinoma. | 3 |
| 30733283 | 2019 | Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma. | 21 |
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
