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Gene Review

Ets1  -  E26 avian leukemia oncogene 1, 5' domain

Mus musculus

Synonyms: AI196000, AI448617, D230050P06, Ets-1, Protein C-ets-1, ...
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Disease relevance of Ets1


High impact information on Ets1

  • Here we demonstrate a role for the Ets1 and Ets2 transcription factors based on their ability to activate the p16INK4a promoter through an ETS-binding site and their patterns of expression during the lifespan of human diploid fibroblasts [6].
  • Here we show, by using RAG-2-deficient blastocyst complementation, that Ets-1 deficiency has dramatic, but different, effects on development and function of T- and B-lineage cells [7].
  • To study the role of Ets-1 in T-cell development and function we have used the RAG-2-/- complementation system and murine embryonic stem (ES) cells containing homozygous deletions in the Ets-1 gene (Ets-1-/-) [8].
  • Following T-cell activation, the specific DNA binding activity of Ets-1 is inactivated by transient phosphorylation, suggesting a function in the transition from the resting to activated state [7].
  • In contrast, Ets-1-deficient B cells were present in normal numbers but a large proportion were IgM plasma cells [7].

Chemical compound and disease context of Ets1

  • Antagonizing Ets-1 might be of benefit in attenuating CCN2 expression in fibrosis, arthritis and cancer, and may be useful in modulating the outcome of these disorders [9].

Biological context of Ets1

  • To investigate the possibility that Ets1 and Ets2 are transcriptional activators, we analyzed the ability of these proteins to trans-activate promoter/enhancer sequences in transient co-transfection experiments [2].
  • We show that mouse ES cells lacking Ets1 are deficient in their ability to undergo UV-induced apoptosis, similar to p53 null ES cells [10].
  • The Ets1 transcription factor is widely expressed during murine embryo development and is associated with mesodermal cells involved in morphogenetic processes such as organ formation [11].
  • Our data show that Ets1 expression increases in embryos after implantation and during organogenesis such that it is expressed in all the organs of day-15 embryos studied [11].
  • In later fetal stages, Ets1 expression is predominant in the lymphoid tissues, brain, and organs that are undergoing branching morphogenesis (e.g., lung) but is dramatically reduced in other organs such as the stomach and intestine [11].

Anatomical context of Ets1

  • In view of the high level expression of Ets1 in lymphoid cells, Ets1 could be part of the transcription complex which mediates the response to Tax1 and the control of HTLV-1 replication [2].
  • Ets1 is required for p53 transcriptional activity in UV-induced apoptosis in embryonic stem cells [10].
  • We observed significantly decreased numbers of NK T cells in the thymus, spleen, and liver of Ets1-deficient mice [12].
  • AML1/Runx1 recruits calcineurin to regulate granulocyte macrophage colony-stimulating factor by Ets1 activation [13].
  • This review will examine in detail the role and possible targets of Ets1 and Ets2 in osteoblast differentiation and bone formation [14].

Associations of Ets1 with chemical compounds

  • The former domain can bind in vitro, in a cooperative manner, factors related to nuclear factor 1 and Ets1; the latter domain contains a type 3 directly repeated sequence that was shown to be able to bind the retinoid X and triiodothyronine receptors [15].
  • In vitro interactions between nuclear proteins and uncoupling protein gene promoter reveal several putative transactivating factors including Ets1, retinoid X receptor, thyroid hormone receptor, and a CACCC box-binding protein [15].
  • Thus the multiple functions of RA in bone cells are likely to be mediated in part by Ets1 [14].
  • Using two-dimensional tryptic phosphopeptide analysis and site-directed mutagenesis, we found that Ets1 was phosphorylated on threonine 38, a residue conserved in several Ets proteins [16].
  • In addition, the expression of Ets1 can be induced in MC3T3-E1 and fetal rat calvaria cells by retinoic acid (RA) which is known to exert profound effects on skeletal growth and development, bone turnover, and induce specific cellular responses in bone cells [14].

Physical interactions of Ets1

  • Previously, we identified an Ets-1-binding site located at -49/-47 in the promoter of Pcyt1a as an important transcriptional element involved in basal CTalpha transcription (Sugimoto, H., Sugimoto, S., Tatei, K., Obinata, H., Bakovic, M., Izumi, T., and Vance, D. E. (2003) J. Biol. Chem. 278, 19716-19722) [17].
  • Ets1 bound to two Ets-binding sites located in the proximal region of the VE-cadherin promoter [18].
  • The constructs having a mutant Ets-1 binding site or lacking this site failed to respond to Ets-1 activation of Npr1 gene transcription [19].
  • In this report we show that GST-c-Ets-1 fusion protein binds specifically to the EndoA enhancer unit sequence by gel shift analysis [20].
  • Our results indicate that Ets-1 physically interacts with Blimp-1, which leads to a block in Blimp-1 DNA binding activity and a reduction in the ability of Blimp-1 to repress target genes without interfering with Blimp-1 protein levels [21].

Regulatory relationships of Ets1


Other interactions of Ets1

  • More generally, Ets1 and Ets2 could regulate transcription of cellular genes [2].
  • After synchronizing the cell cycle in NIH3T3 cells, CTalpha mRNA increased at the S-M phase corresponding to an increase of Ets-1 mRNA and a decrease of Net mRNA [17].
  • Heterologous expression studies in Drosophila Schneider cells confirmed that the constitutive expression of this gene is controlled by Ets-1 and requires the presence both of the Sp1 and Sp3 transcription factors [25].
  • In the present work, we have investigated the expression of both c-ets 1 and u-PA, a putative target gene of the Ets 1 proteins, within a biological model which includes both embryonic and tumoral aspects [3].
  • The deletion of the DNA binding and carboxyl-terminal transactivation domains of HIF-2alpha, respectively, created dominant negative mutants that suppressed transactivation by the wild type protein and failed to synergize with Ets-1 [26].

Analytical, diagnostic and therapeutic context of Ets1


  1. Ets-1 is a critical regulator of Ang II-mediated vascular inflammation and remodeling. Zhan, Y., Brown, C., Maynard, E., Anshelevich, A., Ni, W., Ho, I.C., Oettgen, P. J. Clin. Invest. (2005) [Pubmed]
  2. The product of the c-ets-1 proto-oncogene and the related Ets2 protein act as transcriptional activators of the long terminal repeat of human T cell leukemia virus HTLV-1. Bosselut, R., Duvall, J.F., Gégonne, A., Bailly, M., Hémar, A., Brady, J., Ghysdael, J. EMBO J. (1990) [Pubmed]
  3. Involvement of the proto-oncogene c-ets 1 and the urokinase plasminogen activator during mouse implantation and placentation. Grevin, D., Chen, J.H., Raes, M.B., Stehelin, D., Vandenbunder, B., Desbiens, X. Int. J. Dev. Biol. (1993) [Pubmed]
  4. Provirus insertion in Tpl-1, an Ets-1-related oncogene, is associated with tumor progression in Moloney murine leukemia virus-induced rat thymic lymphomas. Bear, S.E., Bellacosa, A., Lazo, P.A., Jenkins, N.A., Copeland, N.G., Hanson, C., Levan, G., Tsichlis, P.N. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  5. Expression of a 91-kilodalton PEA3-binding protein is down-regulated during differentiation of F9 embryonal carcinoma cells. Martin, M.E., Yang, X.Y., Folk, W.R. Mol. Cell. Biol. (1992) [Pubmed]
  6. Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence. Ohtani, N., Zebedee, Z., Huot, T.J., Stinson, J.A., Sugimoto, M., Ohashi, Y., Sharrocks, A.D., Peters, G., Hara, E. Nature (2001) [Pubmed]
  7. Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene. Bories, J.C., Willerford, D.M., Grévin, D., Davidson, L., Camus, A., Martin, P., Stéhelin, D., Alt, F.W. Nature (1995) [Pubmed]
  8. Defective activation and survival of T cells lacking the Ets-1 transcription factor. Muthusamy, N., Barton, K., Leiden, J.M. Nature (1995) [Pubmed]
  9. The induction of CCN2 by TGFbeta1 involves Ets-1. Van Beek, J.P., Kennedy, L., Rockel, J.S., Bernier, S.M., Leask, A. Arthritis Res. Ther. (2006) [Pubmed]
  10. Ets1 is required for p53 transcriptional activity in UV-induced apoptosis in embryonic stem cells. Xu, D., Wilson, T.J., Chan, D., De Luca, E., Zhou, J., Hertzog, P.J., Kola, I. EMBO J. (2002) [Pubmed]
  11. The Ets1 transcription factor is widely expressed during murine embryo development and is associated with mesodermal cells involved in morphogenetic processes such as organ formation. Kola, I., Brookes, S., Green, A.R., Garber, R., Tymms, M., Papas, T.S., Seth, A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  12. Cutting edge: the Ets1 transcription factor is required for the development of NK T cells in mice. Walunas, T.L., Wang, B., Wang, C.R., Leiden, J.M. J. Immunol. (2000) [Pubmed]
  13. AML1/Runx1 recruits calcineurin to regulate granulocyte macrophage colony-stimulating factor by Ets1 activation. Liu, H., Holm, M., Xie, X.Q., Wolf-Watz, M., Grundström, T. J. Biol. Chem. (2004) [Pubmed]
  14. Ets transcription factors and targets in osteogenesis. Raouf, A., Seth, A. Oncogene (2000) [Pubmed]
  15. In vitro interactions between nuclear proteins and uncoupling protein gene promoter reveal several putative transactivating factors including Ets1, retinoid X receptor, thyroid hormone receptor, and a CACCC box-binding protein. Cassard-Doulcier, A.M., Larose, M., Matamala, J.C., Champigny, O., Bouillaud, F., Ricquier, D. J. Biol. Chem. (1994) [Pubmed]
  16. Phosphorylation of Ets1 regulates the complementation of a CSF-1 receptor impaired in mitogenesis. Rabault, B., Roussel, M.F., Quang, C.T., Ghysdael, J. Oncogene (1996) [Pubmed]
  17. Sp1 is a co-activator with Ets-1, and Net is an important repressor of the transcription of CTP:phosphocholine cytidylyltransferase alpha. Sugimoto, H., Okamura, K., Sugimoto, S., Satou, M., Hattori, T., Vance, D.E., Izumi, T. J. Biol. Chem. (2005) [Pubmed]
  18. ETS1 lowers capillary endothelial cell density at confluence and induces the expression of VE-cadherin. Lelièvre, E., Mattot, V., Huber, P., Vandenbunder, B., Soncin, F. Oncogene (2000) [Pubmed]
  19. Transcriptional regulation of guanylyl cyclase/natriuretic peptide receptor-A gene. Kumar, P., Arise, K.K., Pandey, K.N. Peptides (2006) [Pubmed]
  20. Sequence specific binding of Ets-1 to the mouse cytokeratin EndoA gene enhancer. Hamazato, F., Fujimura, Y., Tamai, Y., Takemoto, Y., Matsushiro, A., Nozaki, M. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  21. Ets-1 regulates plasma cell differentiation by interfering with the activity of the transcription factor Blimp-1. John, S.A., Clements, J.L., Russell, L.M., Garrett-Sinha, L.A. J. Biol. Chem. (2008) [Pubmed]
  22. Basal transcription of the mouse sarco(endo)plasmic reticulum Ca2+-ATPase type 3 gene in endothelial cells is controlled by Ets-1 and Sp1. Hadri, L., Ozog, A., Soncin, F., Lompré, A.M. J. Biol. Chem. (2002) [Pubmed]
  23. Transcriptional regulation of mouse delta-opioid receptor gene: role of Ets-1 in the transcriptional activation of mouse delta-opioid receptor gene. Sun, P., Loh, H.H. J. Biol. Chem. (2001) [Pubmed]
  24. The role of Ets-1 in mast cell granulocyte-macrophage colony-stimulating factor expression and activation. McKinlay, L.H., Tymms, M.J., Thomas, R.S., Seth, A., Hasthorpe, S., Hertzog, P.J., Kola, I. J. Immunol. (1998) [Pubmed]
  25. Gene transcription of fgl2 in endothelial cells is controlled by Ets-1 and Oct-1 and requires the presence of both Sp1 and Sp3. Liu, M., Leibowitz, J.L., Clark, D.A., Mendicino, M., Ning, Q., Ding, J.W., D'Abreo, C., Fung, L., Marsden, P.A., Levy, G.A. Eur. J. Biochem. (2003) [Pubmed]
  26. Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha ) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). Elvert, G., Kappel, A., Heidenreich, R., Englmeier, U., Lanz, S., Acker, T., Rauter, M., Plate, K., Sieweke, M., Breier, G., Flamme, I. J. Biol. Chem. (2003) [Pubmed]
  27. Tandem Sp1/Sp3 sites together with an Ets-1 site cooperate to mediate alpha11 integrin chain expression in mesenchymal cells. Lu, N., Heuchel, R., Barczyk, M., Zhang, W.M., Gullberg, D. Matrix Biol. (2006) [Pubmed]
  28. The RING finger protein RNF11 is expressed in bone cells during osteogenesis and is regulated by Ets1. Gao, Y., Ganss, B.W., Wang, H., Kitching, R.E., Seth, A. Exp. Cell Res. (2005) [Pubmed]
  29. The stress-activated protein kinase subfamily of c-Jun kinases. Kyriakis, J.M., Banerjee, P., Nikolakaki, E., Dai, T., Rubie, E.A., Ahmad, M.F., Avruch, J., Woodgett, J.R. Nature (1994) [Pubmed]
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