A CBP INTEGRATOR COMPLEX MEDIATES TRANSCRIPTIONAL ACTIVATION AND AP-1INHIBITION BY NUCLEAR RECEPTORS

Nuclear receptors regulate gene expression by direct activation of tar get genes and inhibition of AP-1. Here we report that, unexpectedly, a ctivation by nuclear receptors requires the actions of CREB-binding pr otein (CBP) and that inhibition of AP-1 activity is the apparent resul t of competition for limiting amounts of CBP/p300 in cells. Utilizing distinct domains, CBP directly interacts with the ligand-binding domai n of multiple nuclear receptors and with the p160 nuclear receptor coa ctivators, 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 sig nal transduction pathways within the nucleus.