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Letters to Nature

Nature 370, 226-229 (21 July 1994) | doi:10.1038/370226a0; Accepted 21 June 1994

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

J. Arias*, A. S. Alberts†§, P. Brindle*, F. X. Claret‡, T. Smeal‡, M. Karin‡, J. Feramisco†‡ & M. Montminy*

  1. *The Clayton Foundation Laboratories for Peptide Biology,The Salk Institute, La Jolla, California 92037, USA
  2. †, Department of Medicine, ‡Program in Biomedical Sciences, University of California at San Diego, La Jolla,California 92093-0636, USA
  3. §Transcription Laboratory, Imperial Cancer Research Fund,PO Box 123, Lincoln's Inn Fields, London WC2A 3PX, UK
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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.