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

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