Culture serum-induced conversion from agonist to antagonist of a Vitamin D analog, TEI-9647.
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.
Yamaoka
Kazuyoshi
K
Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
Kim
Mi-sun
MS
Takada
Ichiro
I
Takeyama
Ken-ichi
K
Kamimura
Takashi
T
Kato
Shigeaki
S
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry*; D016895:Culture Media, Serum-Free; D004247:DNA / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051381:Rats; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D013237:Stereoisomerism; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism
D003470:Culture Media; D016895:Culture Media, Serum-Free; D008024:Ligands; D018167:Receptors, Calcitriol; D047490:Retinoid X Receptor alpha; C400545:TEI 9647; D014807:Vitamin D; D004247:DNA; D002117:Calcitriol