THE NUCLEAR HORMONE-RECEPTOR COACTIVATOR SRC-1 IS A SPECIFIC TARGET OF P300

p300 and its family member, CREB-binding protein (CBP), function as ke y transcriptional coactivators by virtue of their interaction with the activated forms of certain transcription factors, In a search for add itional cellular targets of p300/CBP, a protein-protein cloning strate gy, surprisingly identified SRC-1, a coactivator involved in nuclear h ormone receptor transcriptional activity, as a p300/CBP interactive pr otein, p300 and SRC-1 interact, specifically, in vitro and they also f orm complexes in vivo, Moreover, we show that SRC-1 encodes a new memb er of the basic helix-loop-helix-PAS domain family and that it physica lly interacts with the retinoic acrid receptor in response to hormone binding, Together, these results Implicate p300 as a component of the retinoic acid signaling pathway, operating, In part, through specific interaction with a nuclear hormone receptor coactivator, SRC-1.