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

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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