ERG (gene)

Source: Wikipedia, the free encyclopedia.
ERG
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 21: 38.38 – 38.66 MbChr 16: 95.16 – 95.39 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

ERG (ETS-related gene) is an

differentiation, angiogenesis, inflammation, and apoptosis
.

Function

Transcriptional regulator ERG is a nuclear protein that binds

white blood cells). Therefore, ERG may act as a regulator of differentiation of early hematopoietic cells.[11]

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.[12] 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.[13]

Cancer

This gene can be classified as a

Ewing's sarcoma and acute myeloid leukemias respectively and function as transcriptional activators.[15][16] ERG and its fusion proteins EWS-ERG and TLS/FUS-ERG inhibit apoptosis.[17] 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.[18]

TMPRSS2 gene fusion

ERG can fuse with

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.[19] 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.[19] In 90% of prostate cancers overexpressing ERG, they also possess a fusion TMPRSS2-ERG protein, suggesting that this fusion is the predominant subtype in prostate cancer.[20]

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.[8]

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.[21]

Location

ERG is located on chromosome 21.[6] The ERG protein is expressed at a similar level throughout the body.[8]

Interactions

ERG has been shown to

interact
with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000157554 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040732 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. PMID 3476934
    .
  6. ^ .
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  8. ^ a b c d "ERG ETS transcription factor ERG [Homo sapiens (Human)] - Gene - NCBI".
  9. PMID 1766675
    .
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  14. ^ "Gene Cards".
  15. ^
    PMID 8084618
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Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.