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Gene Review

ETV1  -  ets variant 1

Homo sapiens

Synonyms: ER81, ETS translocation variant 1, Ets-related protein 81
 
 
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Disease relevance of ETV1

 

High impact information on ETV1

  • ER81 and GABP alpha were present in most tissues of adult mice, whereas ER71 was restricted to testis [7].
  • GABP alpha, ER71, and ER81 recognized the common pentanucleotide DNA sequence 5'-CGGAA/T-3'. Although subtle differences were observed for nucleotide preferences flanking this pentanucleotide core, the overall similarity of the selected sequences was most striking [7].
  • LPP can also functionally interact in a similar manner with the related family member ER81 [8].
  • Collectively, our data elucidated a mechanism whereby three prominent oncoproteins, HER2/Neu, Ras, and Raf, may facilitate tumor formation by inducing hTERT expression in nonimmortalized cells via the transcription factor ER81 [9].
  • Whereas p300 acetylates two lysine residues (K33 and K116) within the ER81 N-terminal transactivation domain, P/CAF targets only K116 [10].
 

Chemical compound and disease context of ETV1

  • Furthermore, the receptor tyrosine kinase HER2/Neu, an oncoprotein particularly found overexpressed in breast tumors, cooperates with both ACTR and p300 to stimulate ER81-mediated transcription [11].
 

Biological context of ETV1

  • In human, the alternative splicing of the ETV1 gene leads to the presence (ETV1 alpha) or the absence (ETV1 beta) of exon 5 encoding the C-terminal part of the transcriptional acidic domain, but without affecting the alpha helix previously described as crucial for transactivation [12].
  • We demonstrated here that the truncated isoform (human ETV1 beta) and the full-length isoform (human ETV1 alpha) bind similarly specific DNA Ets binding sites [12].
  • By screening a genomic DNA library, we characterized the intron-exon junction within the acidic domain of human ER81 and we showed that this junction corresponds to the site where the remaining AA of the acidic domain of ETV1 or mouse ER81 are inserted [13].
  • This gene, designated ETV1 (for ETS Translocation Variant), is located on chromosome band 7p22 [2].
  • We demonstrate how this approach led to the identification of gene fusions of the 5'-untranslated region of TMPRSS2 (21q22.3), an androgen regulated gene, with the ETS transcription factor family members, either ERG (21q22.2), ETV1 (7p21.2), or ETV4(17q21) [14].
 

Anatomical context of ETV1

 

Associations of ETV1 with chemical compounds

  • In one of two androgen-sensitive xenografts, fusion transcripts of TMPRSS2 and ETV1 were detected [1].
  • Database searches revealed that ETV1 mRNA is highly similar to human ER81 described here, although it contains the full-length acidic domain present in mouse ER81 [13].
  • Two serine residues, ER81 amino acids 191 and 216, were identified as MK2 phosphorylation sites [18].
  • Concerted activation of ETS protein ER81 by p160 coactivators, the acetyltransferase p300 and the receptor tyrosine kinase HER2/Neu [11].
 

Physical interactions of ETV1

  • Furthermore, ER81 interacts with one ETS binding site in the Her2/neu promoter, whose mutation decreases ER81-mediated transcription [19].
  • Consistently, MSK1 interacts with two homologous coactivators of ER81, CBP and p300, and stimulates the transactivation domains of CBP [20].
 

Regulatory relationships of ETV1

  • Here, we have analyzed whether, on the other hand, ER81 may regulate the Her2/neu gene [19].
  • Altogether, MK2 may regulate ER81 transcriptional activity in a cell type-specific manner and thereby modulate various physiological processes beyond stress responses [18].
  • MSK1 expression enhances ER81-dependent transcription upon stimulation of especially the p38-MAPK pathway [20].
 

Other interactions of ETV1

  • No TMPRSS2/ETV1 chimeric fusion was detected in this series [21].
  • We investigated mechanisms of expression of four ETS genes, ERG, ETV1, ETV4, and FLI1, in 11 xenografts representing different stages of prostate cancer [1].
  • Here, we also examined effects of EWS-ETV1 and EWS-ERG on expression of the TGF-beta RII gene [22].
  • Cotransfection of these fusion genes and the TGF-beta RII promoter suppresses TGF-beta RII promoter activity and also FLI1-, ERG-, or ETV1-induced promoter activity [22].
  • In this study, we identified a novel interaction partner of ACTR, the ETS transcription factor ER81 that is also heavily implicated in mammary tumor formation [11].
 

Analytical, diagnostic and therapeutic context of ETV1

References

  1. TMPRSS2:ERG Fusion by Translocation or Interstitial Deletion Is Highly Relevant in Androgen-Dependent Prostate Cancer, But Is Bypassed in Late-Stage Androgen Receptor-Negative Prostate Cancer. Hermans, K.G., van Marion, R., van Dekken, H., Jenster, G., van Weerden, W.M., Trapman, J. Cancer Res. (2006) [Pubmed]
  2. A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Jeon, I.S., Davis, J.N., Braun, B.S., Sublett, J.E., Roussel, M.F., Denny, C.T., Shapiro, D.N. Oncogene (1995) [Pubmed]
  3. HER2/Neu- and TAK1-mediated up-regulation of the transforming growth factor beta inhibitor Smad7 via the ETS protein ER81. Dowdy, S.C., Mariani, A., Janknecht, R. J. Biol. Chem. (2003) [Pubmed]
  4. Gene expression profiling of the bone marrow mononuclear cells from patients with myelodysplastic syndrome. Qian, J., Chen, Z., Wang, W., Cen, J., Xue, Y. Oncol. Rep. (2005) [Pubmed]
  5. TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. Cerveira, N., Ribeiro, F.R., Peixoto, A., Costa, V., Henrique, R., Jer??nimo, C., Teixeira, M.R. Neoplasia (2006) [Pubmed]
  6. ETV1 is a novel androgen receptor-regulated gene that mediates prostate cancer cell invasion. Cai, C., Hsieh, C.L., Omwancha, J., Zheng, Z., Chen, S.Y., Baert, J.L., Shemshedini, L. Mol. Endocrinol. (2007) [Pubmed]
  7. Specificities of protein-protein and protein-DNA interaction of GABP alpha and two newly defined ets-related proteins. Brown, T.A., McKnight, S.L. Genes Dev. (1992) [Pubmed]
  8. The LIM domain protein LPP is a coactivator for the ETS domain transcription factor PEA3. Guo, B., Sallis, R.E., Greenall, A., Petit, M.M., Jansen, E., Young, L., Van de Ven, W.J., Sharrocks, A.D. Mol. Cell. Biol. (2006) [Pubmed]
  9. Upregulation of the Catalytic Telomerase Subunit by the Transcription Factor ER81 and Oncogenic HER2/Neu, Ras, or Raf. Goueli, B.S., Janknecht, R. Mol. Cell. Biol. (2004) [Pubmed]
  10. Acetylation-mediated transcriptional activation of the ETS protein ER81 by p300, P/CAF, and HER2/Neu. Goel, A., Janknecht, R. Mol. Cell. Biol. (2003) [Pubmed]
  11. Concerted activation of ETS protein ER81 by p160 coactivators, the acetyltransferase p300 and the receptor tyrosine kinase HER2/Neu. Goel, A., Janknecht, R. J. Biol. Chem. (2004) [Pubmed]
  12. Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human. Coutte, L., Monté, D., Imai, K., Pouilly, L., Dewitte, F., Vidaud, M., Adamski, J., Baert, J.L., de Launoit, Y. Oncogene (1999) [Pubmed]
  13. Molecular characterization of the ets-related human transcription factor ER81. Monté, D., Coutte, L., Baert, J.L., Angeli, I., Stéhelin, D., de Launoit, Y. Oncogene (1995) [Pubmed]
  14. Bioinformatics approach leads to the discovery of the TMPRSS2:ETS gene fusion in prostate cancer. Rubin, M.A., Chinnaiyan, A.M. Lab. Invest. (2006) [Pubmed]
  15. Phylogenetically interrelated ETS genes, ETV1, ERM and E1A-F locate on different chromosomes. Jeon, I.S., Shapiro, D.N. J. Korean Med. Sci. (1998) [Pubmed]
  16. Phosphorylation of ETS transcription factor ER81 in a complex with its coactivators CREB-binding protein and p300. Papoutsopoulou, S., Janknecht, R. Mol. Cell. Biol. (2000) [Pubmed]
  17. Putative regulation of expression of members of the Ets variant 4 transcription factor family and their downstream targets in the rat epididymis. Yang, L., Fox, S.A., Kirby, J.L., Troan, B.V., Hinton, B.T. Biol. Reprod. (2006) [Pubmed]
  18. Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase 2. Janknecht, R. J. Biol. Chem. (2001) [Pubmed]
  19. Regulation of Her2/neu promoter activity by the ETS transcription factor, ER81. Bosc, D.G., Janknecht, R. J. Cell. Biochem. (2002) [Pubmed]
  20. Regulation of the ER81 transcription factor and its coactivators by mitogen- and stress-activated protein kinase 1 (MSK1). Janknecht, R. Oncogene (2003) [Pubmed]
  21. Three-color FISH analysis of TMPRSS2/ERG fusions in prostate cancer indicates that genomic microdeletion of chromosome 21 is associated with rearrangement. Yoshimoto, M., Joshua, A.M., Chilton-Macneill, S., Bayani, J., Selvarajah, S., Evans, A.J., Zielenska, M., Squire, J.A. Neoplasia (2006) [Pubmed]
  22. EWS-FLI1, EWS-ERG, and EWS-ETV1 oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor beta type II receptor gene. Im, Y.H., Kim, H.T., Lee, C., Poulin, D., Welford, S., Sorensen, P.H., Denny, C.T., Kim, S.J. Cancer Res. (2000) [Pubmed]
  23. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Tomlins, S.A., Rhodes, D.R., Perner, S., Dhanasekaran, S.M., Mehra, R., Sun, X.W., Varambally, S., Cao, X., Tchinda, J., Kuefer, R., Lee, C., Montie, J.E., Shah, R.B., Pienta, K.J., Rubin, M.A., Chinnaiyan, A.M. Science (2005) [Pubmed]
  24. Localization of a novel locus for alopecia with mental retardation syndrome to chromosome 3q26.33-q27.3. John, P., Ali, G., Chishti, M.S., Naqvi, S.M., Leal, S.M., Ahmad, W. Hum. Genet. (2006) [Pubmed]
 
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