A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors.
Kamei Y,
Xu L,
Heinzel T,
Torchia J,
Kurokawa R,
Gloss B,
Lin SC,
Heyman RA,
Rose DW,
Glass CK,
Rosenfeld MG.
Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla, 92093-0648, USA.
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.
PMID: 8616895 [PubMed - indexed for MEDLINE]