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Culture serum-induced conversion from agonist to antagonist of a Vitamin D analog, TEI-9647 |
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| Authors: | Yamaoka Kazuyoshi Kim Mi-sun Takada Ichiro Takeyama Ken-ichi Kamimura Takashi Kato Shigeaki |
| Institution: | aInstitute of Molecular and Cellular Biosciences,University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan bExploratory Research for Advanced Technology, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan cTeijin Institute for Biomedical Research, Teijin Pharma Limited, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan |
| Abstract: | The nuclear receptor for Vitamin D (VDR) mediates many of the effects of Vitamin D in target tissues by regulating gene expression. The transactivation function of ligand-bound VDR in target tissues is thought to depend on the tissue-type and the cellular-environment, but the molecular basis for these differences has not been fully understood. In this study, during characterization of TEI-9647 as a synthetic ligand for the VDR, we found that depletion of serum from the culture medium converted TEI-9647 from an antagonist to an agonist of VDR-mediated transactivation, whereas it retained antagonistic activity in the presence of serum. Consistent with these results, using a mammalian two-hybrid system, we found that TEI-9647 recruited different coactivators to the VDR in the presence and absence of serum. These findings suggest that an unknown serum factor modulates the transactivation function of the VDR. |
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