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Ets2  -  E26 avian leukemia oncogene 2, 3' domain

Mus musculus

Synonyms: AU022856, Ets-2, Protein C-ets-2
 
 
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Disease relevance of Ets2

  • Activation of Ets2 at Thr-72 acts in the stroma, downstream of vascular endothelial growth factor production, in part through the regulation of macrophage proteases to support the progression of Neu- and polyomavirus middle-T-initiated mammary tumors [1].
  • 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 [2].
  • Our results raise the possibility of Ets-2 involvement in ovarian pathology seen in patients with Down's syndrome [3].
  • Deletion mutants of E1A and Ets-2 lacking the conserved motif were unable to bind the CBP SID [4].
  • The effect of overexpression of Bcl-xL and Ets-2 proteins on ALN-induced osteoclast apoptosis was determined using an in vitro osteoclast survival assay and retrovirus transfer approach [5].
 

High impact information on Ets2

  • Ablation of the docking site in Ets-1 and Ets-2 prevented Ras pathway-mediated enhancement of the transactivation function of these proteins [6].
  • Defective trophoblast function in mice with a targeted mutation of Ets2 [7].
  • Ectopic expression of Ets2 in the deficient fibroblasts restores expression of both matrix metalloproteinases [7].
  • Targeted deletion of the conserved DNA binding domain of the Ets2 transcription factor results in the retardation and death of homozygous mouse embryos before 8.5 days of embryonic development [7].
  • Rescued Ets2-deficient mice are viable and fertile but have wavy hair, curly whiskers, and abnormal hair follicle shape and arrangement, resembling mice with mutations of the EGF receptor or its ligands [7].
 

Chemical compound and disease context of Ets2

 

Biological context of Ets2

 

Anatomical context of Ets2

  • The size of tumors transplanted into fat pads of mice with Ets2 targeted alleles was correlated directly with Ets2 activity and fewer stromal cells expressing matrix metalloproteinase 9 (MMP-9) [1].
  • The Ets2 transcription factor is constitutively phosphorylated on residue Thr(72) in macrophages derived from mice homozygous for the motheaten viable (me-v) allele of the hemopoietic cell phosphatase (Hcph) gene [11].
  • We show that the expression of c-Myc, an Ets2 target, is elevated in T cells freshly isolated from thymi of ets2 transgenic mice pretreated with dexamethasone [13].
  • In this study, we investigated the effects of Ets2 expression on the proliferation, maturation, and survival of thymocytes by establishing transgenic mice that specifically express Ets2 or a dominant negative form of Ets2, Deltaets2, in the thymus [13].
  • Here we have tested genetically, with the use of a conditional Ets2flox allele and tissue specific Cre recombinase expression, whether Ets2 also functions within tumor cells by inactivating Ets2 within mammary luminal epithelial cells from which transgenic PyMTY315/322F tumors arise [14].
 

Associations of Ets2 with chemical compounds

  • Further deletion constructs (starting with -117/+74) showed a significant reduction in promoter activity when co-transfected with Ets-2 or exposed to LPS [15].
  • Tumor necrosis factor prevents alendronate-induced osteoclast apoptosis in vivo by stimulating Bcl-xL expression through Ets-2 [5].
  • A central role for Ets-2 in the transcriptional regulation and cyclic adenosine 5'-monophosphate responsiveness of the human chorionic gonadotropin-beta subunit gene [16].
 

Physical interactions of Ets2

 

Regulatory relationships of Ets2

  • To further delineate the role of Ets-2 in regulating HO-1 transcription, we performed HO-1 promoter analysis studies in macrophages [15].
  • These data show that Ets-2 related protein binds and activates the EndoA enhancer in a sequence-specific fashion [19].
 

Other interactions of Ets2

 

Analytical, diagnostic and therapeutic context of Ets2

  • We generated by gene targeting a single codon mutation in Ets2 substituting Ala for the critical Thr-72 phosphorylation site (Ets2A72), to investigate the importance of MAP kinase activation of Ets2 in embryo and tumor development [1].
  • In order to address the developmental function of Ets2, we have examined its expression pattern in E8.5 to E13.5 embryos using RNA whole-mount in situ hybridization [12].

References

  1. Ets2-dependent stromal regulation of mouse mammary tumors. Man, A.K., Young, L.J., Tynan, J.A., Lesperance, J., Egeblad, M., Werb, Z., Hauser, C.A., Muller, W.J., Cardiff, R.D., Oshima, R.G. Mol. Cell. Biol. (2003) [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. Ets-1 and Ets-2 protooncogene expression in theca cells of the adult mouse ovary. Rowe, A., Propst, F. Exp. Cell Res. (1992) [Pubmed]
  4. A Conserved alpha-helical motif mediates the binding of diverse nuclear proteins to the SRC1 interaction domain of CBP. Matsuda, S., Harries, J.C., Viskaduraki, M., Troke, P.J., Kindle, K.B., Ryan, C., Heery, D.M. J. Biol. Chem. (2004) [Pubmed]
  5. Tumor necrosis factor prevents alendronate-induced osteoclast apoptosis in vivo by stimulating Bcl-xL expression through Ets-2. Zhang, Q., Badell, I.R., Schwarz, E.M., Boulukos, K.E., Yao, Z., Boyce, B.F., Xing, L. Arthritis Rheum. (2005) [Pubmed]
  6. An ERK2 docking site in the Pointed domain distinguishes a subset of ETS transcription factors. Seidel, J.J., Graves, B.J. Genes Dev. (2002) [Pubmed]
  7. Defective trophoblast function in mice with a targeted mutation of Ets2. Yamamoto, H., Flannery, M.L., Kupriyanov, S., Pearce, J., McKercher, S.R., Henkel, G.W., Maki, R.A., Werb, Z., Oshima, R.G. Genes Dev. (1998) [Pubmed]
  8. Molecular profiling of mouse lung tumors: association with tumor progression, lung development, and human lung adenocarcinomas. Bonner, A.E., Lemon, W.J., Devereux, T.R., Lubet, R.A., You, M. Oncogene (2004) [Pubmed]
  9. A single targeted Ets2 allele restricts development of mammary tumors in transgenic mice. Neznanov, N., Man, A.K., Yamamoto, H., Hauser, C.A., Cardiff, R.D., Oshima, R.G. Cancer Res. (1999) [Pubmed]
  10. Physical and comparative mapping of distal mouse chromosome 16. 5 p5. Cabin, D.E., McKee-Johnson, J.W., Matesic, L.E., Wiltshire, T., Rue, E.E., Mjaatvedt, A.E., Huo, Y.K., Korenberg, J.R., Reeves, R.H. Genome Res. (1998) [Pubmed]
  11. Activated Ets2 is required for persistent inflammatory responses in the motheaten viable model. Wei, G., Guo, J., Doseff, A.I., Kusewitt, D.F., Man, A.K., Oshima, R.G., Ostrowski, M.C. J. Immunol. (2004) [Pubmed]
  12. Ets2 is expressed during morphogenesis of the somite and limb in the mouse embryo. Ristevski, S., Tam, P.P., Hertzog, P.J., Kola, I. Mech. Dev. (2002) [Pubmed]
  13. The role of the Ets2 transcription factor in the proliferation, maturation, and survival of mouse thymocytes. Zaldumbide, A., Carlotti, F., Pognonec, P., Boulukos, K.E. J. Immunol. (2002) [Pubmed]
  14. Ets2-dependent microenvironmental support of mouse mammary tumors. Tynan, J.A., Wen, F., Muller, W.J., Oshima, R.G. Oncogene (2005) [Pubmed]
  15. Role of Ets-2 in the regulation of heme oxygenase-1 by endotoxin. Chung, S.W., Chen, Y.H., Perrella, M.A. J. Biol. Chem. (2005) [Pubmed]
  16. A central role for Ets-2 in the transcriptional regulation and cyclic adenosine 5'-monophosphate responsiveness of the human chorionic gonadotropin-beta subunit gene. Ghosh, D., Ezashi, T., Ostrowski, M.C., Roberts, R.M. Mol. Endocrinol. (2003) [Pubmed]
  17. Interaction between PU.1 and another Ets family transcription factor promotes macrophage-specific Basal transcription initiation. Ross, I.L., Yue, X., Ostrowski, M.C., Hume, D.A. J. Biol. Chem. (1998) [Pubmed]
  18. Involvement of Ets transcription factors and targets in osteoblast differentiation and matrix mineralization. Vary, C.P., Li, V., Raouf, A., Kitching, R., Kola, I., Franceschi, C., Venanzoni, M., Seth, A. Exp. Cell Res. (2000) [Pubmed]
  19. One of two Ets-binding sites in the cytokeratin EndoA enhancer is essential for enhancer activity and binds to Ets-2 related proteins. Fujimura, Y., Yamamoto, H., Hamazato, F., Nozaki, M. Nucleic Acids Res. (1994) [Pubmed]
  20. 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]
 
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