A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors.
Nuclear receptors regulate gene expression by direct activation of target genes and inhibition of AP-1. Here we report that, unexpectedly, activation by nuclear receptors requires the actions of CREB-binding protein (CBP) and that inhibition of AP-1 activity is the apparent result of competition for limiting amounts of CBP/p300 in cells. Utilizing distinct domains, CBP directly interacts with the ligand-binding domain of multiple nuclear receptors and with the p160 nuclear receptor coactivators, which upon cloning have proven to be variants of the SRC-1 protein. Because CBP represents a common factor, required in addition to distinct coactivators for function of nuclear receptors, CREB, and AP-1, we suggest that CBP/p300 serves as an integrator of multiple signal transduction pathways within the nucleus.
Kamei
Y
Y
Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla, 92093-0648, USA.
Xu
L
L
Heinzel
T
T
Torchia
J
J
Kurokawa
R
R
Gloss
B
B
Lin
S C
SC
Heyman
R A
RA
Rose
D W
DW
Glass
C K
CK
Rosenfeld
M G
MG
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive / Q000235:genetics; D050882:CREB-Binding Protein; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D051548:Histone Acetyltransferases; D008024:Ligands; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D056920:Nuclear Receptor Coactivator 1; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*
D018076:DNA, Complementary; D008024:Ligands; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1