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ACTIVATION OF CAMP AND MITOGEN RESPONSIVE GENES RELIES ON A COMMON NUCLEAR FACTOR
Author(s): ARIAS J, ALBERTS AS, BRINDLE P, CLARET FX, SMEAL T, KARIN M, FERAMISCO J, MONTMINY M
Source: NATURE    Volume: 370    Issue: 6486    Pages: 226-229    Published: JUL 21 1994  
Times Cited: 605     References: 21     
Abstract: A NUMBER of Signalling pathways stimulate transcription of target genes through nuclear factors whose activities are primarily regulated 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 Ser133(1,2) Although phosphorylation may stimulate transcriptional 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 necessary for cAMP regulated transcription. We report here that microinjection 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.
Document Type: Article
Language: English
Reprint Address: ARIAS, J (reprint author), SALK INST BIOL STUDIES, CLAYTON FDN LABS PEPTIDE BIOL, 10010 N TORREY PINES RD, LA JOLLA, CA 92037 USA
Addresses:
1. UNIV CALIF SAN DIEGO, DEPT MED, LA JOLLA, CA 92093 USA
2. UNIV CALIF SAN DIEGO, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA
3. IMPERIAL CANC RES FUND, TRANSCRIPT LAB, LONDON WC2A 3PX, ENGLAND
Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW
Subject Category: Multidisciplinary Sciences
IDS Number: NX971
ISSN: 0028-0836
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