* 164873

ETS VARIANT TRANSCRIPTION FACTOR 3; ETV3


Alternative titles; symbols

ETS VARIANT GENE 3
ONCOGENE PE1; PE1
MITOGENIC ETS TRANSCRIPTIONAL SUPPRESSOR; METS


HGNC Approved Gene Symbol: ETV3

Cytogenetic location: 1q23.1     Genomic coordinates (GRCh38): 1:157,121,191-157,138,395 (from NCBI)


TEXT

Cloning and Expression

The ETS oncogene (164720) was first described as part of a fusion gene transduced by the avian retrovirus E26. In E26, v-ets and v-myb (189990) were fused to a portion of GAG to form the transforming gene. The ETS oncogene family shares a conserved peptide motif called the ETS domain that mediates sequence-specific DNA binding. This motif is unique among transcription factor families. Using partially degenerate oligonucleotides from conserved regions of the ETS domain and the polymerase chain reaction, Klemsz et al. (1994) isolated a new member of the ETS family, designated PE1, from HL60 cells. The PE1 gene was expressed as an approximately 5-kb transcript in most cell lines tested.


Gene Function

Klappacher et al. (2002) described a mechanism in which induction of the ETS repressor METS links terminal differentiation to cell cycle arrest. Using macrophages as a model, they provided evidence that METS blocks RAS (190020)-dependent proliferation without inhibiting RAS-dependent expression of cell type-specific genes by selectively replacing ETS activators on the promoters of cell cycle control genes. The antiproliferative effects of METS required its interaction with DP103 (DDX20; 606168), a DEAD box-containing protein that assembles a novel corepressor complex. Functional interactions between the METS/DP103 complex and E2F (see 189971)/RB1 (614041) family proteins were also necessary for inhibition of cellular proliferation, suggesting a combinatorial code that directs permanent cell cycle exit during terminal differentiation.

By screening Il10 (124092)-deficient mouse macrophages early after stimulation with lipopolysaccharide (LPS) alone or with LPS and IL10, followed by studies in human macrophages, El Kasmi et al. (2007) found that IL10 induced ETV3 and SBNO2 (615729) expression. IL10-mediated induction of ETV3 and SBNO2 depended on STAT3 (102582) and Toll-like receptor stimulation. ETV3 expression was induced by the STAT3 pathway after activation by IL10, but not by IL6 (147620), which cannot induce the antiinflammatory signaling pathway. SBNO2 and ETV3 repressed transcription of NFKB (see 164011), but not IRF7 (605047). El Kasmi et al. (2007) proposed that ETV3 and SBNO2 are components of the pathways contributing to the downstream antiinflammatory effects of IL10.


Mapping

Using both in situ hybridization and study of human/hamster cell hybrids, Klemsz et al. (1994) demonstrated that the PE1 gene is located on 1q21-q23.


REFERENCES

  1. El Kasmi, K. C., Smith, A. M., Williams, L., Neale, G., Panopolous, A., Watowich, S. S., Hacker, H., Foxwell, B. M. J., Murray, P. J. Cutting edge: a transcriptional repressor and corepressor induced by the STAT3-regulated anti-inflammatory signaling pathway. J. Immun. 179: 7215-7219, 2007. Note: Erratum: J. Immun. 180: 3612 only, 2008. [PubMed: 18025162, related citations] [Full Text]

  2. Klappacher, G. W., Lunyak, V. V., Sykes, D. B., Sawka-Verhelle, D., Sage, J., Brard, G., Ngo, S. D., Gangadharan, D., Jacks, T., Kamps, M. P., Rose, D. W., Rosenfeld, M. G. An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation. Cell 109: 169-180, 2002. [PubMed: 12007404, related citations] [Full Text]

  3. Klemsz, M., Hromas, R., Raskind, W., Bruno, E., Hoffman, R. PE-1, a novel ETS oncogene family member, localizes to chromosome 1q21-q23. Genomics 20: 291-294, 1994. [PubMed: 8020980, related citations] [Full Text]


Paul J. Converse - updated : 04/23/2014
Stylianos E. Antonarakis - updated : 5/3/2002
Creation Date:
Victor A. McKusick : 4/4/1994
carol : 01/25/2021
mgross : 04/23/2014
mcolton : 4/3/2014
carol : 6/17/2011
mgross : 5/3/2002
mgross : 5/3/2002
carol : 1/5/1999
carol : 4/4/1994

* 164873

ETS VARIANT TRANSCRIPTION FACTOR 3; ETV3


Alternative titles; symbols

ETS VARIANT GENE 3
ONCOGENE PE1; PE1
MITOGENIC ETS TRANSCRIPTIONAL SUPPRESSOR; METS


HGNC Approved Gene Symbol: ETV3

Cytogenetic location: 1q23.1     Genomic coordinates (GRCh38): 1:157,121,191-157,138,395 (from NCBI)


TEXT

Cloning and Expression

The ETS oncogene (164720) was first described as part of a fusion gene transduced by the avian retrovirus E26. In E26, v-ets and v-myb (189990) were fused to a portion of GAG to form the transforming gene. The ETS oncogene family shares a conserved peptide motif called the ETS domain that mediates sequence-specific DNA binding. This motif is unique among transcription factor families. Using partially degenerate oligonucleotides from conserved regions of the ETS domain and the polymerase chain reaction, Klemsz et al. (1994) isolated a new member of the ETS family, designated PE1, from HL60 cells. The PE1 gene was expressed as an approximately 5-kb transcript in most cell lines tested.


Gene Function

Klappacher et al. (2002) described a mechanism in which induction of the ETS repressor METS links terminal differentiation to cell cycle arrest. Using macrophages as a model, they provided evidence that METS blocks RAS (190020)-dependent proliferation without inhibiting RAS-dependent expression of cell type-specific genes by selectively replacing ETS activators on the promoters of cell cycle control genes. The antiproliferative effects of METS required its interaction with DP103 (DDX20; 606168), a DEAD box-containing protein that assembles a novel corepressor complex. Functional interactions between the METS/DP103 complex and E2F (see 189971)/RB1 (614041) family proteins were also necessary for inhibition of cellular proliferation, suggesting a combinatorial code that directs permanent cell cycle exit during terminal differentiation.

By screening Il10 (124092)-deficient mouse macrophages early after stimulation with lipopolysaccharide (LPS) alone or with LPS and IL10, followed by studies in human macrophages, El Kasmi et al. (2007) found that IL10 induced ETV3 and SBNO2 (615729) expression. IL10-mediated induction of ETV3 and SBNO2 depended on STAT3 (102582) and Toll-like receptor stimulation. ETV3 expression was induced by the STAT3 pathway after activation by IL10, but not by IL6 (147620), which cannot induce the antiinflammatory signaling pathway. SBNO2 and ETV3 repressed transcription of NFKB (see 164011), but not IRF7 (605047). El Kasmi et al. (2007) proposed that ETV3 and SBNO2 are components of the pathways contributing to the downstream antiinflammatory effects of IL10.


Mapping

Using both in situ hybridization and study of human/hamster cell hybrids, Klemsz et al. (1994) demonstrated that the PE1 gene is located on 1q21-q23.


REFERENCES

  1. El Kasmi, K. C., Smith, A. M., Williams, L., Neale, G., Panopolous, A., Watowich, S. S., Hacker, H., Foxwell, B. M. J., Murray, P. J. Cutting edge: a transcriptional repressor and corepressor induced by the STAT3-regulated anti-inflammatory signaling pathway. J. Immun. 179: 7215-7219, 2007. Note: Erratum: J. Immun. 180: 3612 only, 2008. [PubMed: 18025162] [Full Text: https://doi.org/10.4049/jimmunol.179.11.7215]

  2. Klappacher, G. W., Lunyak, V. V., Sykes, D. B., Sawka-Verhelle, D., Sage, J., Brard, G., Ngo, S. D., Gangadharan, D., Jacks, T., Kamps, M. P., Rose, D. W., Rosenfeld, M. G. An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation. Cell 109: 169-180, 2002. [PubMed: 12007404] [Full Text: https://doi.org/10.1016/s0092-8674(02)00714-6]

  3. Klemsz, M., Hromas, R., Raskind, W., Bruno, E., Hoffman, R. PE-1, a novel ETS oncogene family member, localizes to chromosome 1q21-q23. Genomics 20: 291-294, 1994. [PubMed: 8020980] [Full Text: https://doi.org/10.1006/geno.1994.1169]


Contributors:
Paul J. Converse - updated : 04/23/2014
Stylianos E. Antonarakis - updated : 5/3/2002

Creation Date:
Victor A. McKusick : 4/4/1994

Edit History:
carol : 01/25/2021
mgross : 04/23/2014
mcolton : 4/3/2014
carol : 6/17/2011
mgross : 5/3/2002
mgross : 5/3/2002
carol : 1/5/1999
carol : 4/4/1994