Abstract
The vitamin D Receptor (VDR) belongs to the superfamily of steroid/thyroid hormone receptors that is activated by 1α,25-dihydroxyvitamin D3. Traditional targets for 1α,25-dihydroxyvitamin D3 action include tissues involved in the maintenance of calcium homeostasis and bone development and remodeling. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a transcriptional coactivator that plays a role in mitochondrial biogenesis and energy metabolism, is predominantly expressed in kidney, heart, liver, and skeletal muscle. Because VDR and PGC-1α display an overlapping pattern of expression, we investigated the possibility that PGC-1α could serve as a coactivator for VDR. Transient cotransfection assays demonstrate that PGC-1α augments ligand-dependent VDR transcription when either full-length VDR or Gal4 DNA binding domain-VDR-ligand binding domain chimeras were analyzed. Furthermore, mammalian two-hybrid assays, coimmunoprecipitation analyses, and biochemical coactivator recruitment assays demonstrate a ligand-dependent interaction between the two proteins both in cells and in vitro. The coactivation potential of PGC-1α requires an intact AF-2 domain of VDR and the LXXLL motif in PGC-1α. Taken together, these results indicate that PGC-1α serves as a coactivator for VDR.
- Received March 9, 2005.
- Accepted May 20, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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