ERG (gene)

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Protein-coding gene in the species Homo sapiens

title: "ERG (gene)" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["transcription-factors", "oncogenes"] description: "Protein-coding gene in the species Homo sapiens" topic_path: "arts/film" source: "https://en.wikipedia.org/wiki/ERG_(gene)" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

ERG (ETS-related gene) is an oncogene. ERG is a member of the ETS (erythroblast transformation-specific) family of transcription factors. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis.

Function

Transcriptional regulator ERG is a nuclear protein that binds purine-rich sequences of DNA. Transcriptional regulator ERG is required for platelet adhesion to the subendothelium and regulates hematopoiesis. It has a DNA binding domain and a PNT (pointed) domain.

The Mld2 mutation, generated through an ENU mutagenesis screen, was the first non-functional allele of Erg. Homozygous Mld2 is embryonic lethal at day 13.5. Adult mice heterozygous for the Mld2 mutation have hematopoietic stem cell defects. This means that when the ERG gene was not actively transcribed and the ERG protein produced, a mouse's hematopoietic cells were unable to function properly. Since ERG is important to the ability of the hematopoietic cells to function and self-renew, there may be applications in using blood stem cells for tissue repair, transplantation and other therapeutic applications.

Cancer

This gene can be classified as a proto-oncogene. During chromosomal translocations that occur in cell division, ERG can be transposed onto another chromosome. This results in gene fusion products, which can lead to unregulated cell proliferation. Examples of these fusion gene products would be TMPRSS2-ERG and NDRG1-ERG in prostate cancer, EWS-ERG in Ewing’s sarcoma, and FUS-ERG in acute myeloid leukemia. DNA binding protein ERG fuses with RNA binding proteins EWS and TLS/FUS in Ewing's sarcoma and acute myeloid leukemias respectively and function as transcriptional activators. ERG and its fusion proteins EWS-ERG and TLS/FUS-ERG inhibit apoptosis. Morpholino splice-switching oligonucleotides have been used to induce exon 4 skipping in prostate cancer cell lines, mouse models and tissue explants, leading to anti-cancer effects, including reduction of proliferation and induction of apoptosis.

TMPRSS2 gene fusion

ERG can fuse with TMPRSS2 protein to form an oncogenic fusion gene that is commonly found in human prostate cancer, especially in hormone-refractory prostate cancer. This suggests that ERG overexpression may contribute to development of androgen-independence in prostate cancer through disruption of androgen receptor signaling. The fusion gene is critical to the progression of cancer because it inhibits the androgen receptor expression and it binds and inhibits androgen receptors already present in the cell. Essentially TMPRSS2-ERG fusion disrupts the ability of the cells to differentiate into proper prostate cells creating unregulated and unorganized tissue.

EWS gene fusion

Ewing's sarcoma is associated with chromosomal translocations, which typically results in fusion genes with transcriptional regulators. This means that the protein transcribes for with the gene could be produced in excess or under- produced resulting in unnatural activity in cells. Typically this is the first step in a cell's progression to malignancy. In about 10% of Ewing's Sarcoma cases have an EWS1-ERG fusion.

Fusion with TLS/FUS

In acute myeloid leukemia, the t(16;21) translocation in myeloid leukemia fuses TLS/FUS to ERG which disrupts the natural TLS/FUS RNA binding domain, and instead inserting the ERG DNA binding domain.

Location

ERG is located on chromosome 21. The ERG protein is expressed at a similar level throughout the body.

Interactions

ERG has been shown to interact with:

References

References

  1. (Sep 1987). "The erg gene: a human gene related to the ets oncogene". Proceedings of the National Academy of Sciences of the United States of America.
  2. (Aug 1987). "erg, a human ets-related gene on chromosome 21: alternative splicing, polyadenylation, and translation". Science.
  3. (Nov 1988). "The human erg gene maps to chromosome 21, band q22: relationship to the 8; 21 translocation of acute myelogenous leukemia". Oncogene.
  4. "ERG ETS transcription factor ERG [Homo sapiens (Human)] - Gene - NCBI".
  5. (Dec 1991). "erg, an ets-related gene, codes for sequence-specific transcriptional activators". Oncogene.
  6. (Jul 1993). "Characterization of the DNA binding and transcriptional activation domains of the erg protein". Oncogene.
  7. (Jun 1993). "Human ERG-2 protein is a phosphorylated DNA-binding protein--a distinct member of the ets family". Oncogene.
  8. (Jul 2008). "The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells". Nature Immunology.
  9. (Feb 2011). "ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification". Genes & Development.
  10. "Gene Cards").
  11. (Oct 1994). "The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains". Oncogene.
  12. (Dec 1994). "TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain". Oncogene.
  13. (Mar 1997). "Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias". Oncogene.
  14. (2020-06-25). "Targeting the ERG oncogene with splice-switching oligonucleotides as a novel therapeutic strategy in prostate cancer". British Journal of Cancer.
  15. (2008). "Role of the TMPRSS2-ERG gene fusion in prostate cancer". Neoplasia.
  16. (Jun 1994). "An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation". Cancer Research.
  17. (May 2001). "Identification of amino acid residues in the ETS transcription factor Erg that mediate Erg-Jun/Fos-DNA ternary complex formation". The Journal of Biological Chemistry.
  18. (Oct 1997). "The Ets transcription factors interact with each other and with the c-Fos/c-Jun complex via distinct protein domains in a DNA-dependent and -independent manner". The Journal of Biological Chemistry.
  19. (May 2010). "An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression". Cancer Cell.
  20. (Mar 2014). "Ablation of the oncogenic transcription factor ERG by deubiquitinase inhibition in prostate cancer". Proc Natl Acad Sci USA.

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transcription-factorsoncogenes