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Activation of TR4 orphan nuclear receptor gene promoter by cAMP/PKA and C/EBP signaling

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Abstract

In earlier studies, we had suggested that the fasting signal induces TR4 orphan nuclear receptor expression in vivo. The detailed mechanism(s), however, remain unclear. In this study, we found that cAMP/PKA, the mediator of fasting and glucagon signals, could induce TR4 gene expression that in turn modulates gluconeogenesis. Mechanistic dissection by in vitro studies in hepatocytes demonstrated that cAMP/PKA might trigger C/EBP α and β binding to the selective cAMP response element, which is located at the TR4 promoter, thus inducing TR4 transcription. We also demonstrated that the binding activity of C/EBPs to the TR4 promoter is increased in response to cAMP treatment. Together, our data identified a new signaling pathway from the fasting signal → cAMP/PKA → C/EBP α and β → TR4 → gluconeogenesis in hepatocytes; and suggested that TR4 could be an important regulator to control glucose homeostasis. The identification of activator(s)/inhibitor(s) or ligand(s) of TR4 may provide us an alternative way to control gluconeogenesis.

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References

  1. B.S. Skalhegg, K. Tasken, Front. Biosci. 5, D678–D693 (2000)

    Article  CAS  PubMed  Google Scholar 

  2. W.J. Roesler, Mol. Cell. Endocrinol. 162, 1–7 (2000)

    Article  CAS  PubMed  Google Scholar 

  3. D. Yeagley, J.M. Agati, P.G. Quinn, J. Biol. Chem. 273, 18743–18750 (1998)

    Article  CAS  PubMed  Google Scholar 

  4. M. Giralt, E.A. Park, A.L. Gurney, J.S. Liu, P. Hakimi, R.W. Hanson, J. Biol. Chem. 266, 21991–21996 (1991)

    CAS  PubMed  Google Scholar 

  5. Y. Olswang, H. Cohen, O. Papo, H. Cassuto, C.M. Croniger, P. Hakimi, S.M. Tilghman, R.W. Hanson, L. Reshef, Proc. Natl Acad. Sci. USA 99, 625–630 (2002)

    Article  CAS  PubMed  Google Scholar 

  6. N.C. Liu, W.J. Lin, E. Kim, L.L. Collins, H.Y. Lin, I.C. Yu, J.D. Sparks, L.M. Chen, Y.F. Lee, C. Chang, Diabetes 56, 2901–2909 (2007)

    Article  CAS  PubMed  Google Scholar 

  7. H. Gronemeyer, J.A. Gustafsson, V. Laudet, Nat. Rev. Drug Discov. 3, 950–964 (2004)

    Article  CAS  PubMed  Google Scholar 

  8. E. Kim, S. Xie, S.D. Yeh, Y.F. Lee, L.L. Collins, Y.C. Hu, C.R. Shyr, X.M. Mu, N.C. Liu, Y.T. Chen, P.H. Wang, C. Chang, J. Biol. Chem. 278, 46919–46926 (2003)

    Article  CAS  PubMed  Google Scholar 

  9. S. Inui, Y.F. Lee, A.R. Haake, L.A. Goldsmith, C. Chang, J. Invest. Dermatol. 112, 426–431 (1999)

    Article  CAS  PubMed  Google Scholar 

  10. R.M. Tombes, M.O. Faison, J.M. Turbeville, Gene 322, 17–31 (2003)

    Article  CAS  PubMed  Google Scholar 

  11. M. Wegner, Z. Cao, M.G. Rosenfeld, Science 256, 370–373 (1992)

    Article  CAS  PubMed  Google Scholar 

  12. R.W. Hanson, L. Reshef, Annu. Rev. Biochem. 66, 581–611 (1997)

    Article  CAS  PubMed  Google Scholar 

  13. W.J. Roesler, Annu. Rev. Nutr. 21, 141–165 (2001)

    Article  CAS  PubMed  Google Scholar 

  14. I. Penuelas, I.J. Encio, N. Lopez-Moratalla, E. Santiago, J. Steroid Biochem. Mol. Biol. 67, 89–94 (1998)

    Article  CAS  PubMed  Google Scholar 

  15. F.A. Kruyt, G. Folkers, C.E. van den Brink, P.T. van der Saag, Nucleic Acids Res. 20, 6393–6399 (1992)

    Article  CAS  PubMed  Google Scholar 

  16. L. Pei, H. Waki, B. Vaitheesvaran, D.C. Wilpitz, I.J. Kurland, P. Tontonoz, Nat. Med. 12, 1048–1055 (2006)

    Article  CAS  PubMed  Google Scholar 

  17. M.D. Huq, P. Gupta, N.P. Tsai, L.N. Wei, Mol. Cell. Proteomics 5, 2072–2082 (2006)

    Article  CAS  PubMed  Google Scholar 

  18. M.C. Carmona, E. Hondares, M.L. Rodriguez de la Concepcion, V. Rodriguez-Sureda, J. Peinado-Onsurbe, V. Poli, R. Iglesias, F. Villarroya, M. Giralt, Biochem. J. 389, 47–56 (2005)

    Article  CAS  PubMed  Google Scholar 

  19. L. Qiao, O.A. MacDougald, J. Shao, J. Biol. Chem. 281, 24390–24397 (2006)

    Article  CAS  PubMed  Google Scholar 

  20. M.H. Kim, R. Nakayama, P. Manos, J.E. Tomlinson, E. Choi, J.D. Ng, D. Holten, J. Lipid Res. 30, 663–671 (1989)

    CAS  PubMed  Google Scholar 

  21. K.L. Wyne, J.R. Schreiber, A.L. Larsen, G.S. Getz, J. Biol. Chem. 264, 981–989 (1989)

    CAS  PubMed  Google Scholar 

  22. A.F. Gombart, U. Krug, J. O’Kelly, E. An, V. Vegesna, H.P. Koeffler, J. Leukoc. Biol. 78, 1153–1165 (2005)

    Article  CAS  PubMed  Google Scholar 

  23. M. Mangeney, P. Cardot, S. Lyonnet, C. Coupe, R. Benarous, A. Munnich, J. Girard, J. Chambaz, G. Bereziat, Eur. J. Biochem. 181, 225–230 (1989)

    Article  CAS  PubMed  Google Scholar 

  24. Y.F. Lee, H.J. Pan, J.P. Burbach, E. Morkin, C. Chang, J. Biol. Chem. 272, 12215–12220 (1997)

    Article  CAS  PubMed  Google Scholar 

  25. D.B. Jump, A. Bell, G. Lepar, D. Hu, Mol. Endocrinol. 4, 1655–1660 (1990)

    Article  CAS  PubMed  Google Scholar 

  26. J.D. Shuman, T. Sebastian, P. Kaldis, T.D. Copeland, S. Zhu, R.C. Smart, P.F. Johnson, Mol. Cell. Biol. 24, 7380–7391 (2004)

    Article  CAS  PubMed  Google Scholar 

  27. M. Miller, J.D. Shuman, T. Sebastian, Z. Dauter, P.F. Johnson, J. Biol. Chem. 278, 15178–15184 (2003)

    Article  CAS  PubMed  Google Scholar 

  28. G. Li, Y.F. Lee, S. Liu, Y. Cai, S. Xie, N.C. Liu, B.Y. Bao, Z. Chen, C. Chang, Endocrinology 149, 3490–3499 (2008)

    Article  CAS  PubMed  Google Scholar 

  29. K.E. Boyd, P.J. Farnham, Mol. Cell. Biol. 19, 8393–8399 (1999)

    CAS  PubMed  Google Scholar 

  30. Y. Shang, X. Hu, J. DiRenzo, M.A. Lazar, M. Brown, Cell 103, 843–852 (2000)

    Article  CAS  PubMed  Google Scholar 

  31. M.K. Bennett, T.F. Osborne, Proc. Natl Acad. Sci. USA 97, 6340–6344 (2000)

    Article  CAS  PubMed  Google Scholar 

  32. K.J. Livak, T.D. Schmittgen, Methods 25, 402–408 (2001)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We are gratefully indebted to Dr. Peter F Johnson for his help in kindly providing C/EBP plasmid constructs. We also thank K. Wolf for her help in preparation of the manuscript for this article.

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Authors and Affiliations

  1. George Whipple Laboratory for Cancer Research, Department of Pathology and Urology, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Ning-Chun Liu, Wen-Jye Lin, I-Chen Yu, Hung-Yun Lin, Su Liu, Yi-Fen Lee & Chawnshang Chang

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  1. Ning-Chun Liu
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  2. Wen-Jye Lin
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  3. I-Chen Yu
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  4. Hung-Yun Lin
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  5. Su Liu
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Correspondence to Chawnshang Chang.

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Liu, NC., Lin, WJ., Yu, IC. et al. Activation of TR4 orphan nuclear receptor gene promoter by cAMP/PKA and C/EBP signaling. Endocr 36, 211–217 (2009). https://doi.org/10.1007/s12020-009-9220-0

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  • DOI: https://doi.org/10.1007/s12020-009-9220-0

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