Vitamin D receptor and nuclear receptor coactivators: crucial interactions in vitamin D-mediated transcription.
The nuclear actions of 1,25-dihydroxyvitamin D(3) [1alpha,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 1alpha,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 1alpha,25(OH)(2)D(3) and the VDR.
MacDonald
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Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA. pnm2@po.cwru.edu
Baudino
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Tokumaru
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Dowd
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DR
Zhang
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C
D000818:Animals; D006801:Humans; D018167:Receptors, Calcitriol / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects*; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology*
D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014807:Vitamin D