Takeyama K, Masuhiro Y, Fuse H, Endoh H, Murayama A, Kitanaka S, Suzawa M, Yanagisawa J, Kato S
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113, Japan.
Mol Cell Biol. 1999 Feb;19(2):1049-55. doi: 10.1128/MCB.19.2.1049.
The nuclear vitamin D receptor (VDR) is a member of a nuclear receptor superfamily and acts as a ligand-dependent transcription factor. A family of cotranscriptional activators (SRC-1, TIF2, and AIB-1) interacts with and activates the transactivation function of nuclear receptors in a ligand-dependent way. We examined interaction of VDR with these coactivators that was induced by several vitamin D analogs, since they exert differential subsets of the biological action of vitamin D through unknown mechanisms. Unlike other vitamin D analogs tested, OCT (22-oxa-1alpha,25-dihydroxyvitamin D3) induced interaction of VDR with TIF2 but not with SRC-1 or AIB-1. Consistent with these interactions, only TIF2 was able to potentiate the transactivation function of VDR bound to OCT. Thus, the present findings suggest that the structure of VDR is altered in a vitamin D analog-specific way, resulting in selective interactions of VDR with coactivators. Such selective interaction of coactivators with VDR may specify the array of biological actions of a vitamin D analog like OCT, possibly through activating a particular set of target gene promoters.
核维生素D受体（VDR）是核受体超家族的成员，作为一种依赖配体的转录因子发挥作用。一类共转录激活因子（SRC-1、TIF2和AIB-1）以依赖配体的方式与核受体相互作用并激活其反式激活功能。我们研究了几种维生素D类似物诱导的VDR与这些共激活因子的相互作用，因为它们通过未知机制发挥维生素D不同的生物学作用子集。与其他测试的维生素D类似物不同，OCT（22-氧杂-1α，25-二羟基维生素D3）诱导VDR与TIF2相互作用，但不与SRC-1或AIB-1相互作用。与这些相互作用一致，只有TIF2能够增强与OCT结合的VDR的反式激活功能。因此，目前的研究结果表明，VDR的结构以维生素D类似物特异性的方式发生改变，导致VDR与共激活因子的选择性相互作用。共激活因子与VDR的这种选择性相互作用可能通过激活特定的一组靶基因启动子来确定像OCT这样的维生素D类似物的生物学作用阵列。
