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EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes

Oncogene volume 19, pages 745–753 (2000)Cite this article

Abstract

ETS1 is a member of the evolutionarily conserved family of ets genes, which are transcription factors that bind to unique DNA sequences, either alone or by association with other proteins. In this study, we have used the yeast two-hybrid system to identify an ETS1 interacting protein. The ETS1 N-terminal amino acid region was used as bait and an interaction was identified with the Daxx protein, referred to as EAP1 (ETS1 Associated Protein 1)/Daxx. This interactin has been shown to exist in yeast and in vitro. EAP1/Daxx and ETS1 are co-localized in the nucleus of mammalian cells. The region in EAP1/Daxx which specifically binds to ETS1 is located within its carboxy terminal 173 amino acid region. The ETS1 interaction region is located within its N-terminal 139 amino acids and is referred as the Daxx Interaction Domain (DID). The DID appears to be conserved in several other ets family members, as well as in other proteins known to interact with Daxx. The EAP1/Daxx interacts with both isoforms of ETS1, p51-ETS1 and p42-ETS1. Interaction of EAP1/Daxx with ETS1 causes the repression of transcriptional activation of the MMP1 and BCL2 genes. The interaction domains of both ETS1 and EAP1/Daxx are required for this repression and deletion of either domain abolishes this activity.

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References

  • Athanasiou M, Clausen PA, Mavrothalassitis GJ, Zhang XK, Watson DK and Blair DG. . 1996 Cell Growth Differ. 7: 1525–1534.

  • Ausubel F, Brent R and Kingston R (eds). . 1995 Current Protocols in Molecular Biology. Wiley Interscience, New York.

    Google Scholar 

  • Barton K, Muthusamy N, Fischer C, Ting CN, Walunas TL, Lanier LL and Leiden JM. . 1998 Immunity 9: 555–563.

    Article  CAS  Google Scholar 

  • Bassuk A and Leiden J. . 1997 Advances in Immunology Vol. 64 Academic Press: San Diego pp. 65–104.

    Google Scholar 

  • Bhat NK, Fischinger PJ, Seth A, Watson DK and Papas T. . 1996 Inter. J. Oncol. 8: 841–846.

  • Bhat NK, Komschlies KL, Fujiwara S, Fisher RJ, Mathieson BJ, Gregorio TA, Young HA, Kasik JW, Ozato K and Papas TS. . 1989 J. Immunol. 142: 672–678.

  • Bhat NK and Papas TS. . 1994 Challenges of Modern Medicine Vol. 5:: Ares-Serono Symposia 5. Verna R and Shamoo A (eds).. pp. 63–68.

  • Bhat NK, Thompson CB, Lindsten T, June CH, Fujiwara S, Koizumi S, Fisher RJ and Papas TS. . 1990 Proc. Natl. Acad. Sci. USA 87: 3723–3727.

  • Bradford AP, Wasylyk C, Wasylyk B and Gutierrezhartmann A. . 1997 Mol. Cell Biol. 17: 1065–1074.

  • Chen HM and Boxer LM. . 1995 Mol. Cell. Biol. 15: 3840–3847.

    Article  CAS  Google Scholar 

  • Dahl E, Koseki H and Balling R. . 1997 Bioessays 19: 755–765.

    Article  CAS  Google Scholar 

  • Fisher AL and Caudy M. . 1998 Genes Dev. 12: 1931–1940.

  • Fitzsimmons D, Hodsdon W, Wheat W, Maira SM, Wasylyk B and Hagman J. . 1996 Genes Dev. 10: 2198–2211.

  • Ghysdael J and Boureux A. . 1997 The ETS family of Transcriptional Regulators. Birkhauser Verlag, Basel, Switzerland.

    Book  Google Scholar 

  • Graves B and Petersen J. . 1998 Advances in Cancer Research Vol. 75. Academic Press: San Diego, California pp. 1–55.

    Google Scholar 

  • Gyuris J, Golemis E, Chertkov H and Brent R. . 1993 Cell 75: 791–803.

    Article  CAS  Google Scholar 

  • Halle JP, Haus-Seuffert P, Woltering C, Stelzer G and Meisterernst M. . 1997 Mol. Cell. Biol. 17: 4220–4229.

    Article  CAS  Google Scholar 

  • Herberg JA, Beck S and Trowsdale J. . 1998 J. Mol. Biol. 277: 839–857.

  • Ho IC, Bhat NK, Gottschalk LR, Lindsten T, Thompson CB, Papas TS and Leiden JM. . 1990 Science 250: 814–818.

    Article  CAS  Google Scholar 

  • Hollenbach AD, Sublett JE, McPherson CJ and Grosveld G. . 1999 EMBO J. 18: 3702–3211.

  • Huang CC, Papas TS and Bhat NK. . 1997 Oncogene 15: 851–856.

    Article  CAS  Google Scholar 

  • Iwasaka C, Tanaka K, Abe M and Sato Y. . 1996 J. Cell Physiol. 169: 522–531.

  • Jorcyk CL, Watson DK, Mavrothalassitis GJ and Papas TS. . 1991 Oncogene 6: 523–532.

  • Kiriakidou M, Driscoll DA, Lopez-Guisa JM and Strauss JF, III. . 1997 DNA Cell Biol. 16: 1289–1298.

  • Lautenberger JA, Burdett LA, Gunnell MA, Qi S, Watson DK, O’Brien SJ and Papas TS. . 1992 Oncogene 7: 1713–1719.

  • Li R, Pei H and Papas TS. . 1999 Proc. Natl. Acad. Sci. USA 96: 3876–3881.

  • Logan SK, Garabedian MJ, Campbell CE and Werb Z. . 1996 J. Biol. Chem. 271: 774–782.

    Article  CAS  Google Scholar 

  • Maroulakou IG, Papas TS and Green JE. . 1994 Oncogene 9: 1551–1565.

  • Oda N, Abe M and Sato Y. . 1999 J. Cell Physiol. 178: 121–132.

  • Pluta AF, Earnshaw WC and Goldberg IG. . 1998 J. Cell Sci. 111: 2029–2041.

  • Pribyl LJ, Watson DK, McWilliams MJ, Ascione R and Papas TS. . 1988 Dev. Biol. 127: 45–53.

  • Pribyl LJ, Watson DK, Schulz RA and Papas TS. . 1991 Oncogene 6: 1175–1183.

  • Rutter JL, Mitchell TI, Buttice G, Meyers J, Gusella JF, Ozelius LJ and Brinckerhoff CE. . 1998 Cancer Res. 58: 5321–5325.

  • Seth A and Papas TS. . 1990 Oncogene 5: 1761–1767.

  • Seth A, Watson DK, Blair DG and Papas TS. . 1989 Proc. Natl. Acad. Sci. USA 86: 7833–7877.

  • Sieweke MH, Tekotte H, Frampton J and Graf T. . 1996 Cell 85: 49–60.

    Article  CAS  Google Scholar 

  • Slupsky CM, Gentile LN, Donaldson LW, Mackereth CD, Seidel JJ, Graves BJ and McIntosh LP. . 1998 Proc. Natl. Acad. Sci. USA 95: 12129–12134.

  • Wasylyk C, Bradford AP, Gutierrez-Hartmann A and Wasylyk B. . 1997 Oncogene 14: 899–913.

    Article  CAS  Google Scholar 

  • Watson DK, McWilliams MJ, Lapis P, Lautenberger JA, Schweinfest CW and Papas TS. . 1998 Proc. Natl. Acad. Sci. USA 85: 7862–7866.

  • Watson DK, Robinson L, Hodge DR, Kola I, Papas TS and Seth A. . 1997 Oncogene 14: 213–221.

    Article  CAS  Google Scholar 

  • Werner MH, Clore M, Fisher CL, Fisher RJ, Trinh L, Shiloach J and Gronenborn AM. . 1995 Cell 83: 761–771.

    Article  CAS  Google Scholar 

  • Wotton D, Ghysdael J, Wang S, Speck NA and Owen MJ. . 1994 Mol. Cell. Biol. 14: 840–850.

    Article  CAS  Google Scholar 

  • Yang X, Khosravi-Far R, Chang HY and Baltimore D. . 1997 Cell 89: 1067–1076.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr R Brent (Harvard Medical School, MA, USA) for generously providing the yeast two hybrid reagents; Dr L Boxer (Stanford University, CA, USA) for providing BCL-2 luciferase reporter plasmid; Drs J Rutter and C Brinckerhoff (Dartmouth Medical School, NH, USA) for the MMP1-luciferase reporter plasmids and Dr M Sieweke (EMBL, Germany) for MafB plasmid. We thank Drs J Vournakis, T Hsu and C Schweinfest for critical review of the manuscript. The GeneBank accession number for the sequence of EAP1/Daxx reported in this paper is AF097742. This work was supported in part by National Institutes of Health Grants P01CA78582, RO1CA76231 and American Cancer Society Grant (GN-164) to TS Papas. This study is dedicated to the memory of Dr Takis S Papas, a mentor, scientific colleague and friend.

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  1. Department of Medicine, Center for Molecular and Structural Biology, and Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, South Carolina, USA

    Runzhao Li, Huiping Pei, Dennis K Watson & Takis S Papas

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  1. Runzhao Li
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Li, R., Pei, H., Watson, D. et al. EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene 19, 745–753 (2000). https://doi.org/10.1038/sj.onc.1203385

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