Vitamin D receptor and nuclear receptor coactivators: crucial interactions in vitamin D-mediated transcription

The nuclear actions of 1,25-dihydroxyvitamin D-3 [1 alpha ,25(OH)(2)D-3] are mediated by the vitamin D receptor (VDR). Binding of ligand induces conformational changes in the VDR which promote heterodimerization with retinoid X receptor (RXR) and recruitment of a number of nuclear receptor coactivator proteins including the steroid receptor coactivator (SRC) family members, select SMAD proteins, a novel coactivator complex referred to as DRIP, and a variety of other putative factors. We recently described a novel nuclear receptor coactivator termed NCoA-62 that interacts with the VDR to enhance 1 alpha ,25(OH)(2)D-3-activated transcription. NCoA-62 is unrelated to the SRC family, the DRIP complex, as well as other nuclear receptor coactivators described thus Far. The molecular mechanisms involved in NCoA-62 coactivator function are poorly understood, but protein-protein interactions are likely to play an important role. The purpose of this paper is to briefly review salient features of the coactivators involved in VDR-activated transcription and to focus: on our current understanding of NCoA-62 and its interplay with other nuclear receptor coactivator proteins. It is clear from the studies described here that a concerted series of interactions with multiple coactivator proteins are essential for high order transactivation by 1 alpha ,25(OH)(2)D-3 and the VDR. (C) 2001 Elsevier Science Inc. All rights reserved.