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Activation of cAMP and mitogen responsive genes relies on a common nuclear factor

Nature volume 370, pages 226–229 (1994)Cite this article

Abstract

A NUMBER of signalling pathways stimulate transcription of target genes through nuclear factors whose activities are primarily regul-ated by phosphorylation. Cyclic AMP regulates the expression of numerous genes, for example, through the protein kinase-A (PKA)-mediated phosphorylation of transcription factor CREB at Ser 1331,2. Although phosphorylation may stimulate transcrip-tional activators by modulating their nuclear transport or DNA-binding affinity3, CREB belongs to a class of proteins whose phosphorylation appears specifically to enhance their trans-activation potential1,2,4. Recent work describing a phospho-CREB binding protein (CBP)5 which interacts specifically with the CREB trans-activation domain prompted us to examine whether CBP is neces-sary for cAMP regulated transcription. We report here that micro-injection of an anti-CBP antiserum into fibroblasts can inhibit transcription from a cAMP responsive promoter. Surprisingly, CBP also cooperates with upstream activators such as c-Jun, which are involved in mitogen responsive transcription6. We propose that CBP is recruited to the promoter through interaction with certain phosphorylated factors, and that CBP may thus play a critical role in the transmission of inductive signals from cell surface receptor to the transcriptional apparatus.

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References

  1. Gonzalez, G. A. & Montminy, M. R. Cell 59, 675–680 (1989).

    Article  CAS  PubMed  Google Scholar 

  2. Lee, C. Q., Yun, Y., Hoeffler, J. P. & Habener, J. F. EMBO J. 9, 4455–4465 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hunter, T. & Karin, M. Cell 70, 375–387 (1992).

    Article  CAS  PubMed  Google Scholar 

  4. Brindle, P., Linke, S. & Montminy, M. Nature 365, 855–858 (1993).

    Article  Google Scholar 

  5. Chrivia, J. C. et al. Nature 365, 855–859 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Angel, P. & Karin, M. Biochem. biophys. Acta 1072, 129–157 (1991).

    CAS  PubMed  Google Scholar 

  7. Hagiwara, M. et al. Cell 70, 105–113 (1992).

    Article  CAS  PubMed  Google Scholar 

  8. Zinck, R., Hipskind, R., Pingoud, V. & Nordheim, A. EMBO J. 12, 2377–2387 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hibi, M., Lin, A., Smeal, T., Minden, A. & Karin, M. Genes Dev. 7, 2135–2148 (1993).

    Article  CAS  PubMed  Google Scholar 

  10. Pulverer, B., Lyriakis, J., Avruch, J., Nikolakaki, E. & Woodgett, J. Nature 353, 670–674 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Smeal, T., Binetruy, B., Mercola, D. A., Birrer, M. & Karin, M. Nature 354, 494–496 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Gille, H., Sharrocks, A. D. & Shaw, P. E. Nature 358, 414–417 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Binetruy, B., Smeal, T. & Karin, M. Nature 351, 122–127 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Derijard, B., et al. Cell 76, 1025–1038 (1994).

    Article  CAS  PubMed  Google Scholar 

  15. Lin, A. et al. Cell 76, 777–789 (1992).

    Article  Google Scholar 

  16. Eckner, R. et al. Genes Dev. 8, 869–884 (1994).

    Article  CAS  PubMed  Google Scholar 

  17. Karin, M. & Smeal, T. Trends biochem. Sci. 17, 418–422 (1992).

    Article  CAS  PubMed  Google Scholar 

  18. Gonzalez, G. A., Menzel, P., Leonard, J., Fischer, W. H. & Montminy, M. R. Molec. cell. Blol. 11, 1306–1312 (1991).

    Article  CAS  Google Scholar 

  19. Alberts, A. S. et al. Molec. cell. Biol. 13, 2104–2112 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Angel, P. et al. Cell 49, 729–739 (1987).

    Article  CAS  PubMed  Google Scholar 

  21. Meinkoth, J., Alberts, A. & Feramisco, J. CIBA Foundation Symp. 150, 47–56 (1990).

    CAS  Google Scholar 

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Authors and Affiliations

  1. The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California, 92037, USA

    J. Arias, P. Brindle & M. Montminy

  2. Department of Medicine, University of California at San Diego, La Jolla, California, 92093-0636, USA

    A. S. Alberts & J. Feramisco

  3. Program in Biomedical Sciences, University of California at San Diego, La Jolla, California, 92093-0636, USA

    F. X. Claret, T. Smeal, M. Karin & J. Feramisco

  4. Transcription Laboratory, Imperial Cancer Research Fund, PO Box 123, Lincoln's Inn Fields, London, WC2A 3PX, UK

    A. S. Alberts

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  1. J. Arias
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  8. M. Montminy
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Arias, J., Alberts, A., Brindle, P. et al. Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature 370, 226–229 (1994). https://doi.org/10.1038/370226a0

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