Identification and characterization of a novel transcriptional activation domain in the CREB-binding protein.
The CREB-binding protein (CBP) plays a central role in the regulation of gene expression by several different second messenger pathways including serum growth factors, cAMP and phorbol esters. CBP specifically binds to the phosphorylated forms of CREB and c-Jun and is thought to activate transcription through a C-terminal activation domain. In this report, we demonstrate that the C terminus of CBP is dispensable for its ability to stimulate phospho-CREB activity, and, further, that the deletion of this domain produces highly active, mutant forms of CBP. The novel N-terminal activation identified by this deletional analysis consists of the first 714 amino acids of CBP and is sufficient for high levels of transcriptional activity. This domain is also capable of stimulating the activity of a second cAMP-regulated factor, ATF-1. Surprisingly, ATF-1 activity is not significantly stimulated by full-length CBP suggesting that the C-terminal domain of CBP may also serve to regulate ATF-1/CBP activity. Additionally, the demonstration that one of our hyperactive CBP mutants is able to activate a nonphosphorylatable mutant of CREB (M1 CREB) provides the first evidence that CBP may play a role in regulating the basal transcriptional activity of CREB.
Bisotto
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Laboratory of Molecular Endocrinology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada H3A 1A1.
Minorgan
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Rehfuss
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RP
D051697:Activating Transcription Factor 1; D001665:Binding Sites; D050882:CREB-Binding Protein; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D035581:Transcription Factor TFIIB; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D051697:Activating Transcription Factor 1; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; D050882:CREB-Binding Protein