EHF (ets homologous factor)

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

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

Identity

HGNC

EHF

LOCATION

11p13

IMAGE

LOCUSID

26298

ALIAS

ESE3,ESE3B,ESEJ

FUSION GENES

Show Gene Fusions

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

Gene ID	Transcript ID	Uniprot
ENSG00000135373	ENST00000257831	Q9NZC4
ENSG00000135373	ENST00000450654	Q9NZC4
ENSG00000135373	ENST00000525253	E9PQR6
ENSG00000135373	ENST00000527935	E9PPS9
ENSG00000135373	ENST00000529527	E9PN75
ENSG00000135373	ENST00000530286	Q9NZC4
ENSG00000135373	ENST00000531728	E9PPS9
ENSG00000135373	ENST00000531794	Q9NZC4
ENSG00000135373	ENST00000532302	E9PQX0
ENSG00000135373	ENST00000533754	Q9NZC4

Expression (GTEx)

100

150

200

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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/js/tumors-explorer/