Skip to main content
SpringerLink
Log in

V-erba homodimers mediate the potent dominant negative activity of v-erba on everted repeats

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The oncoprotein v-erbA is a mutated form of TRα1 that is unable to bind thyroid hormone (T3). V-erbA homodimerizes or heterodimerizes with retinoid X receptor (RXR) on core motifs arranged as direct, everted, or inverted repeats (DRs, ERs, or IRs). We created a series of v-erbA mutants in order to obtain a better understanding of the role of v-erbA homodimers versus v-erbA-RXR heterodimers in the dominant negative activity of v-erbA on ERs (the most potent v-erbA response elements). We found that one of these mutants, v-erbA mutant E325A, is able to homodimerize but unable to heterodimerize with RXR on ERs. Our data also suggest that v-erbA homodimers interact preferentially with the corepressor NCoR over SMRT and that the interaction with corepressors is stronger with v-erbA homodimers over v-erbA-RXR heterodimers. Furthermore, functional studies showed that v-erbA homodimers rather than v-erbA-RXR heterodimers mediate the dominant negative activity of v-erbA on ERs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Evans RM (1988) Science 240, 889–895.

    Google Scholar 

  2. Sap J, Munoz A, Damm K, Goldberg Y, Ghysdael J, Leutz A, Beug H & Vennstrom B (1986) Nature 324: 635–640.

    Google Scholar 

  3. Sharif M & Privalsky ML (1991) Cell 66: 885–893.

    Google Scholar 

  4. Damm K, Thompson CC & Evans RM (1989) Nature 339: 593–597.

    Google Scholar 

  5. Horlein AJ, Naar A, Heinzel T, Torchia J, Gloss B, Kurokawa R, Ryan A, Kamei Y, Soderstrom M, Glass CK & Rosenfeld MG (1995) Nature 377: 397–404.

    Google Scholar 

  6. Chen DJ & Evans RM (1995) Nature 377: 454–457.

    Google Scholar 

  7. Robyr D, Wolffe AP & Wahli W (2000) Mol. Endocrinol. 14: 329–347.

    Google Scholar 

  8. Shen Q & Subauste JS (2000) J. Biol. Chem. 275: 41018–41027.

    Google Scholar 

  9. Subauste JS & Koenig RJ (1998) Mol. Endocrinol. 12: 1380–1392.

    Google Scholar 

  10. Leid M, Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T, Chen JY, Staub A, Garnier JM, Mader S & Chambon P (1992) Cell 68, 377–395.

    Google Scholar 

  11. Hollenberg AN, Monden T, Madura JP, Lee K & Wondisford FE (1996) J. Biol. Chem. 271: 28516–28520.

    Google Scholar 

  12. Chen JD, Umesono K & Evans RM (1996) Proc. Natl. Acad. Sci. USA 93: 7567–7571.

    Google Scholar 

  13. Prost E, Koenig RJ, Moore DD, Larsen PR & Whalen RG (1988) Nucl. Acids Res. 16: 6248.

    Google Scholar 

  14. Subauste JS & Koenig RJ (1995) J. Biol. Chem. 270: 7957–7962.

    Google Scholar 

  15. Prost E & Moore DD (1986) Gene 45: 107–111.

    Google Scholar 

  16. Koenig RJ, Warne RL, Brent GA, Harney JW, Larsen PR & Moore DD (1988) Proc. Natl. Acad. Sci. USA 85: 5031–5035.

    Google Scholar 

  17. Thompson CC & Evans RM (1989) Proc. Natl. Acad. Sci. USA 86: 3494–3498.

    Google Scholar 

  18. Perlmann T, Umesono K, Rangarajan P, Forman BM & Evans RM (1996) Mol. Endocrinol. 10: 958–966.

    Google Scholar 

  19. Zubkova I & Subauste JS (2003) Mol. Cell. Endocrinol. 199: 61–72.

    Google Scholar 

  20. Zechel C, Shen XQ, Chen JY, Chen Z, Chambon P & Gronemeyer H (1994) EMBO J. 13: 1425–1433.

    Google Scholar 

  21. Mader S, Chen JY, Chen Z, White J, Chambon P & Gronemeyer H (1993) EMBO J. 12: 5029–5041.

    Google Scholar 

  22. Umesono K, Murakami KK, Thompson CC & Evans RM (1991) Cell 65: 1255–1266.

    Google Scholar 

  23. Mangelsdorf DJ, Umesono K, Kliewer SA, Borgmeyer U, Ong ES & Evans RM (1991) 66: 555–561.

  24. Mangelsdorf DJ & Evans RM (1995) Cell 83: 841–850.

    Google Scholar 

  25. Cohen RN, Wondisford FE & Hollenberg AN (1998) Mol. Endocrinol. 12: 1567–1581.

    Google Scholar 

  26. Barlow C, Meister B, Lardelli M, Lendahl U & Vennstrom B (1994) EMBO J. 13: 4241–4250.

    Google Scholar 

  27. Feng X, Jiang Y, Metzer P & Yen PM (2000) Mol. Endocrinol. 14: 947–955.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. G.V. Montgomery Veterans Administration Medical Center and Division of Endocrinology and Metabolism, University of Mississippi, Jackson, MS, 39216, USA

    Inna Zubkova & Jose S. Subauste

  2. G.V. Montgomery-VAMC, 1500 E. Woodrow Wilson Blvd., R&E Building (151), Jackson, MS, 39216, USA

    Jose S. Subauste

Authors
  1. Inna Zubkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jose S. Subauste
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zubkova, I., Subauste, J.S. V-erba homodimers mediate the potent dominant negative activity of v-erba on everted repeats. Mol Biol Rep 31, 131–137 (2004). https://doi.org/10.1023/B:MOLE.0000031412.25988.30

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:MOLE.0000031412.25988.30

Search

Navigation