Activation of cAMP and mitogen responsive genes relies on a common nuclear factor (original) (raw)
- Letter
- Published: 21 July 1994
- A. S. Alberts2,4,
- P. Brindle1,
- F. X. Claret3,
- T. Smeal3,
- M. Karin3,
- J. Feramisco2,3 &
- …
- M. Montminy1
Nature volume 370, pages 226–229 (1994)Cite this article
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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
- The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California, 92037, USA
J. Arias, P. Brindle & M. Montminy - Department of Medicine, University of California at San Diego, La Jolla, California, 92093-0636, USA
A. S. Alberts & J. Feramisco - 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 - Transcription Laboratory, Imperial Cancer Research Fund, PO Box 123, Lincoln's Inn Fields, London, WC2A 3PX, UK
A. S. Alberts
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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
- Received: 11 May 1994
- Accepted: 21 June 1994
- Issue Date: 21 July 1994
- DOI: https://doi.org/10.1038/370226a0
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