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Received for publication March 9, 2005.
Revised May 20, 2005.
Accepted for publication May 20, 2005.
Coactivator-1 
(PGC-1)
The Vitamin D Receptor (VDR) belongs to the superfamily of steroid/thyroid hormone receptors that is activated by 1
,25-dihydroxyvitamin D3. Traditional targets for 1,25-dihydroxyvitamin D3 action include tissues involved in the maintenance of calcium homeostasis, bone development and remodeling including the bone, kidney, skeletal and cardiac muscle. PGC-1, a transcriptional coactivator which plays a role in mitochondrial biogenesis and energy metabolism, is predominantly expressed in the kidney, heart, liver and skeletal muscle tissues. Since VDR and PGC-1 display an overlapping pattern of expression, we investigated the possibility that PGC-1 could serve as a coactivator for VDR. Transient cotransfection assays demonstrate that PGC-1 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-1 requires an intact AF-2 domain of VDR and the LXXLL motif in PGC-1. Taken together, these results indicate that PGC-1 serves as a coactivator for VDR.
Key words:
PPARs, Vitamin D
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