Activation of cAMP and mitogen responsive genes relies on a common nuclear factor (original) (raw)

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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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

Authors

  1. J. Arias
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  2. A. S. Alberts
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  3. P. Brindle
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  4. F. X. Claret
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  5. T. Smeal
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  6. M. Karin
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  7. J. Feramisco
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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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