Nuclear protein CBP is a coactivator for the transcription factor CREB.
The transcription factor CREB binds to a DNA element known as the cAMP-regulated enhancer (CRE). CREB is activated through phosphorylation by protein kinase A (PKA), but precisely how phosphorylation stimulates CREB function is unknown. One model is that phosphorylation may allow the recruitment of coactivators which then interact with basal transcription factors. We have previously identified a nuclear protein of M(r)265K, CBP, that binds specifically to the PKA-phosphorylated form of CREB. We have used fluorescence anisotropy measurements to define the equilibrium binding parameters of the phosphoCREB:CBP interaction and report here that CBP can activate transcription through a region in its carboxy terminus. The activation domain of CBP interacts with the basal transcription factor TFIIB through a domain that is conserved in the yeast coactivator ADA-1 (ref. 8). Consistent with its role as a coactivator, CBP augments the activity of phosphorylated CREB to activate transcription of cAMP-responsive genes.
Kwok
R P
RP
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Lundblad
J R
JR
Chrivia
J C
JC
Richards
J P
JP
Bächinger
H P
HP
Brennan
R G
RG
Roberts
S G
SG
Green
M R
MR
Goodman
R H
RH
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D050882:CREB-Binding Protein; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004247:DNA; D004742:Enhancer Elements, Genetic; D005454:Fluorescence Polarization; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins; D013004:Somatostatin / Q000235:genetics; D015534:Trans-Activators; D035581:Transcription Factor TFIIB; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; D013004:Somatostatin; D004247:DNA; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse