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

• Published in: Nature (London) 1994-07, Vol.370 (6486), p.226-229
• Main Authors: Arias, J, Alberts, A. S, Brindle, P, Claret, F. X, Smeal, T, Karin, M, Feramisco, J, Montminy, M
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Ageing, cell death; Amino Acid Sequence; Animals; Biological and medical sciences; Blotting, Western; Cell physiology; CREB-Binding Protein; Cyclic AMP - metabolism; Cyclic AMP Response Element-Binding Protein - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes; Genes, Reporter; Genetics; HeLa Cells; Humanities and Social Sciences; Humans; letter; Mice; Mitogens - metabolism; Molecular and cellular biology; Molecular Sequence Data; multidisciplinary; Nuclear Proteins - immunology; Nuclear Proteins - metabolism; Phosphorylation; Promoter Regions, Genetic; Proteins; Proto-Oncogene Proteins c-jun - genetics; Rabbits; Science; Science (multidisciplinary); Serine - metabolism; Signal Transduction; Trans-Activators; Transcription Factors - immunology; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/370226a0

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 133 1,2 . Although phosphorylation may stimulate transcrip-tional activators by modulating their nuclear transport or DNA-binding affinity 3 , CREB belongs to a class of proteins whose phosphorylation appears specifically to enhance their trans -activation potential 1,2,4 . 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 transcription 6 . 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.