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Gene Review

ETS1  -  v-ets avian erythroblastosis virus E26...

Homo sapiens

Synonyms: ETS-1, EWSR2, FLJ10768, Protein C-ets-1, p54
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Disease relevance of ETS1


High impact information on ETS1


Chemical compound and disease context of ETS1


Biological context of ETS1

  • Late after stimulation, ETS1 mRNA is reinduced and maintained at a high level, while ETS2 gene expression decreases to undetectable levels [12].
  • We have previously shown that ETS transcription factors, regulate cell growth and differentiation, and ETS1 and ETS2 are able to transcriptionally regulate wt p53 gene expression [13].
  • The ETS1 and FLI-1 proteins provide a novel mechanism of activation for GADD153, allowing these two ETS genes to control its expression during cell growth and differentiation, rather than in response to oxidative stress [13].
  • Mutation of the core ETS binding site from -GGAA- to -GGAT- prevents the binding of ETS-like factors with the exception of ETS1 [14].
  • EAPII negatively modulates ETS1 transcriptional activity and attenuates synergistic transactivation by ETS1 and AP-1 [15].

Anatomical context of ETS1


Associations of ETS1 with chemical compounds

  • The expression of the protooncogenes ETS1 and ETS2 has been studied in purified human T cells activated either by cross-linking of the T-cell receptor-CD3 complex on their cell surface or by direct stimulation with phorbol esters and ionomycin [12].
  • In AS ETS1 transfectants, IL-2 formation was completely inhibited by cyclosporin A and FK590 [18].
  • The ETS1 gene encodes a sequence-specific transcription factor binding to purine-rich DNA sequences (-GGAA-) present in the transcriptional regulatory regions of many cellular and viral promoters/enhancers, including many lymphokine genes [18].
  • The IL-2 promoter linked to a chloramphenicol acetyl transferase reporter gene has high activity in AS ETS1 transfectants, indicating that increased IL-2 production seems to be a result of transcriptional induction [18].
  • This threonine residue was neither phosphorylated by JNK1, nor by p38 MAP kinases and was required for the induction of transcriptional activity of ETS1 by HGF/SF [19].

Physical interactions of ETS1

  • SP100 protein interacts with ETS1 both in vitro and in vivo [20].
  • EAPII interacts with ETS1 and modulates its transcriptional function [15].
  • Expression of ETS1 DNA binding domain in Jurkat T cells also decreased the production of IL-2 [18].
  • The region in EAP1/Daxx which specifically binds to ETS1 is located within its carboxy terminal 173 amino acid region [21].
  • In vitro, Sp1 and Ets1 are shown to cooperate to form a ternary complex with the SP1/ERE-A element [22].

Enzymatic interactions of ETS1


Regulatory relationships of ETS1

  • The VEGF-induced invasiveness was inhibited by ETS1 antisense oligonucleotides but not by a sense control [16].
  • SP100 inhibits ETS1 activity in primary endothelial cells [24].
  • Ets1 up-regulated the expression of MMP-1 promoter activity, whereas Fli1 had antagonistic effects on them [25].
  • Addition of Ets1 greatly enhanced the Smad3/TGF beta-mediated activation [26].
  • Furthermore, ETS-1 mediated activation of IKKalpha is negatively regulated by p53 binding to ETS-1 [27].
  • Mechanistic analyses revealed that in endothelial cells EGF/FGF2 signaling induces ETS1 expression, increases HIF-2alpha protein level in absence of hypoxia, and recruits both ETS1 and HIF-2alpha to the VEGFR1 chromatin domain [28].

Other interactions of ETS1

  • Finally, functional studies indicate that transcriptional antagonism exists between NURR1 and ETS1 on the MMP-1 promoter [29].
  • These data demonstrate that SP100 modulates ETS1-dependent biological processes [20].
  • A number of the ETS family of transcription factors are expressed in T cells, including ETS1 and ELF1 [14].
  • The CD3D, G, and E genes have been positioned proximal to the 11q23 breakpoint of the 4;11 translocation while the THY1 and ETS1 genes have been mapped distal to this breakpoint [30].
  • Several HBx mutant proteins unable to bind DDB1 remained competent for transactivation, indicating that HBx binding to DDB1 is not required for HBx transactivation of the ETS1 promoter [31].

Analytical, diagnostic and therapeutic context of ETS1


  1. Rearrangements on chromosome 11q23 in hematopoietic tumor-associated t(11;14) and t(11;19) translocations. Akao, Y., Seto, M., Takahashi, T., Saito, M., Utsumi, K.R., Nakazawa, S., Ueda, R. Cancer Res. (1991) [Pubmed]
  2. Differential regulation of the response to DNA damage in Ewing's sarcoma cells by ETS1 and EWS/FLI-1. Soldatenkov, V.A., Trofimova, I.N., Rouzaut, A., McDermott, F., Dritschilo, A., Notario, V. Oncogene (2002) [Pubmed]
  3. Further localization of ETS1 indicates that the chromosomal rearrangement in Ewing sarcoma does not occur at fra(11)(q23). Simmers, R.N., Sutherland, G.R. Hum. Genet. (1988) [Pubmed]
  4. Molecular analysis of the ets genes and their products. Watson, D.K., Ascione, R., Papas, T.S. Critical reviews in oncogenesis. (1990) [Pubmed]
  5. Expression of ETS proto-oncogenes in astrocytes in human cortex. Amouyel, P., Gégonne, A., Delacourte, A., Défossez, A., Stéhelin, D. Brain Res. (1988) [Pubmed]
  6. Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27. Freshney, N.W., Rawlinson, L., Guesdon, F., Jones, E., Cowley, S., Hsuan, J., Saklatvala, J. Cell (1994) [Pubmed]
  7. Interleukin 1 alpha activates two forms of p54 alpha mitogen-activated protein kinase in rabbit liver. Kracht, M., Truong, O., Totty, N.F., Shiroo, M., Saklatvala, J. J. Exp. Med. (1994) [Pubmed]
  8. HNE interacts directly with JNK isoforms in human hepatic stellate cells. Parola, M., Robino, G., Marra, F., Pinzani, M., Bellomo, G., Leonarduzzi, G., Chiarugi, P., Camandola, S., Poli, G., Waeg, G., Gentilini, P., Dianzani, M.U. J. Clin. Invest. (1998) [Pubmed]
  9. Stable co-occupancy of transcription factors and histones at the HIV-1 enhancer. Steger, D.J., Workman, J.L. EMBO J. (1997) [Pubmed]
  10. ATF-2 is preferentially activated by stress-activated protein kinases to mediate c-jun induction in response to genotoxic agents. van Dam, H., Wilhelm, D., Herr, I., Steffen, A., Herrlich, P., Angel, P. EMBO J. (1995) [Pubmed]
  11. The p54 cleaved form of the tyrosine kinase Lyn generated by caspases during BCR-induced cell death in B lymphoma acts as a negative regulator of apoptosis. Luciano, F., Herrant, M., Jacquel, A., Ricci, J.E., Auberger, P. FASEB J. (2003) [Pubmed]
  12. Reciprocal expression of human ETS1 and ETS2 genes during T-cell activation: regulatory role for the protooncogene ETS1. Bhat, N.K., Thompson, C.B., Lindsten, T., June, C.H., Fujiwara, S., Koizumi, S., Fisher, R.J., Papas, T.S. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  13. Regulation of the human stress response gene GADD153 expression: role of ETS1 and FLI-1 gene products. Seth, A., Giunta, S., Franceschil, C., Kola, I., Venanzoni, M.C. Cell Death Differ. (1999) [Pubmed]
  14. ETS1 transactivates the human GM-CSF promoter in Jurkat T cells stimulated with PMA and ionomycin. Thomas, R.S., Tymms, M.J., Seth, A., Shannon, M.F., Kola, I. Oncogene (1995) [Pubmed]
  15. EAPII interacts with ETS1 and modulates its transcriptional function. Pei, H., Yordy, J.S., Leng, Q., Zhao, Q., Watson, D.K., Li, R. Oncogene (2003) [Pubmed]
  16. Inhibition of vascular endothelial growth factor-induced endothelial cell migration by ETS1 antisense oligonucleotides. Chen, Z., Fisher, R.J., Riggs, C.W., Rhim, J.S., Lautenberger, J.A. Cancer Res. (1997) [Pubmed]
  17. Human ERG is a proto-oncogene with mitogenic and transforming activity. Hart, A.H., Corrick, C.M., Tymms, M.J., Hertzog, P.J., Kola, I. Oncogene (1995) [Pubmed]
  18. Role of ETS1 in IL-2 gene expression. Romano-Spica, V., Georgiou, P., Suzuki, H., Papas, T.S., Bhat, N.K. J. Immunol. (1995) [Pubmed]
  19. Hepatocyte growth factor/scatter factor activates the ETS1 transcription factor by a RAS-RAF-MEK-ERK signaling pathway. Paumelle, R., Tulasne, D., Kherrouche, Z., Plaza, S., Leroy, C., Reveneau, S., Vandenbunder, B., Fafeur, V., Tulashe, D., Reveneau, S. Oncogene (2002) [Pubmed]
  20. SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion. Yordy, J.S., Li, R., Sementchenko, V.I., Pei, H., Muise-Helmericks, R.C., Watson, D.K. Oncogene (2004) [Pubmed]
  21. EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Li, R., Pei, H., Watson, D.K., Papas, T.S. Oncogene (2000) [Pubmed]
  22. Synergistic activation of the HTLV1 LTR Ets-responsive region by transcription factors Ets1 and Sp1. Gégonne, A., Bosselut, R., Bailly, R.A., Ghysdael, J. EMBO J. (1993) [Pubmed]
  23. Ets1 was significantly activated by ERK1/2 in mutant K-ras stably transfected human adrenocortical cells. Chen, Y.F., Shin, S.J., Lin, S.R. DNA Cell Biol. (2005) [Pubmed]
  24. SP100 inhibits ETS1 activity in primary endothelial cells. Yordy, J.S., Moussa, O., Pei, H., Chaussabel, D., Li, R., Watson, D.K. Oncogene (2005) [Pubmed]
  25. Matrix metalloproteinase-1 up-regulation by hepatocyte growth factor in human dermal fibroblasts via ERK signaling pathway involves Ets1 and Fli1. Jinnin, M., Ihn, H., Mimura, Y., Asano, Y., Yamane, K., Tamaki, K. Nucleic Acids Res. (2005) [Pubmed]
  26. Transforming growth factor beta regulates parathyroid hormone-related protein expression in MDA-MB-231 breast cancer cells through a novel Smad/Ets synergism. Lindemann, R.K., Ballschmieter, P., Nordheim, A., Dittmer, J. J. Biol. Chem. (2001) [Pubmed]
  27. Identification and characterization of the IKKalpha promoter: positive and negative regulation by ETS-1 and p53, respectively. Gu, L., Zhu, N., Findley, H.W., Woods, W.G., Zhou, M. J. Biol. Chem. (2004) [Pubmed]
  28. Activation of the VEGFR1 chromatin domain: an angiogenic signal-ETS1/HIF-2alpha regulatory axis. Dutta, D., Ray, S., Vivian, J.L., Paul, S. J. Biol. Chem. (2008) [Pubmed]
  29. Transcriptional Repression of Matrix Metalloproteinase Gene Expression by the Orphan Nuclear Receptor NURR1 in Cartilage. Mix, K.S., Attur, M.G., Al-Mussawir, H., Abramson, S.B., Brinckerhoff, C.E., Murphy, E.P. J. Biol. Chem. (2007) [Pubmed]
  30. CD3G is within 200 kb of the leukemic t(4;11) translocation breakpoint. Das, S., Cotter, F.E., Gibbons, B., Dhut, S., Young, B.D. Genes Chromosomes Cancer (1991) [Pubmed]
  31. Dissociation of DDB1-binding and transactivation properties of the hepatitis B virus X protein. Wentz, M.J., Becker, S.A., Slagle, B.L. Virus Res. (2000) [Pubmed]
  32. Comparative mapping of the constitutional and tumor-associated 11;22 translocations. Budarf, M., Sellinger, B., Griffin, C., Emanuel, B.S. Am. J. Hum. Genet. (1989) [Pubmed]
  33. ETS target genes: identification of egr1 as a target by RNA differential display and whole genome PCR techniques. Robinson, L., Panayiotakis, A., Papas, T.S., Kola, I., Seth, A. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  34. ETS-1 transcription factor binds cooperatively to the palindromic head to head ETS-binding sites of the stromelysin-1 promoter by counteracting autoinhibition. Baillat, D., Bègue, A., Stéhelin, D., Aumercier, M. J. Biol. Chem. (2002) [Pubmed]
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