Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation.
Détails
ID Serval
serval:BIB_A39CFE22FEBF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation.
Périodique
Molecular and cellular biology
ISSN
0270-7306
Statut éditorial
Publié
Date de publication
03/2000
Peer-reviewed
Oui
Volume
20
Numéro
5
Pages
1546-52
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. - Publication Status: ppublish
Résumé
Phosphorylation of the transcription factor CREB leads to the recruitment of the coactivator, CREB binding protein (CBP). Recent studies have suggested that CBP recruitment is not sufficient for CREB function, however. We have identified a conserved protein-protein interaction motif within the CBP-binding domains of CREB and another transcription factor, SREBP (sterol-responsive element binding protein). In contrast to CREB, SREBP interacts with CBP in the absence of phosphorylation. We have exploited the conservation of this interaction motif to test whether CBP recruitment to CREB is sufficient for transcriptional activation. Substitution of six nonconserved amino acids from SREBP into the activation domain of CREB confers high-affinity, phosphorylation-independent CBP binding. The mutated CREB molecule, CREB(DIEDML), activates transcription in F9 teratocarcinoma and PC12 cells even in the absence of protein kinase A (PKA). Addition of exogenous CBP augments the level of transcription mediated by CREB(DIEDML), and adenovirus 12S E1A blocks transcription, implicating CBP in the activation process. Thus, recruitment of CBP to CREB is sufficient for transcriptional activation. Addition of PKA stimulates transcription induced by CREB(DIEDML) further, suggesting that a phosphorylation event downstream from CBP recruitment augments CREB signaling.
Mots-clé
Amino Acid Sequence, CREB-Binding Protein, Cyclic AMP Response Element-Binding Protein, Gene Expression Regulation, Humans, Molecular Sequence Data, Mutation, Nuclear Proteins, Sequence Alignment, Signal Transduction, Trans-Activators, Transcription, Genetic, Transcriptional Activation, Tumor Cells, Cultured
Pubmed
Web of science
Création de la notice
18/02/2008 11:32
Dernière modification de la notice
20/08/2019 16:09