Genomic actions of 1,25-dihydroxyvitamin D3.
Genomic actions of 1,25-dihydroxyvitamin D3.
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DOI：
10.1093/jn/125.suppl_6.1690s
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发表时间：
1995-06
期刊：
影响因子：
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通讯作者：
G. Whitfield;J. Hsieh;P. Jurutka;S. Selznick;C. Haussler;P. MacDonald;M. Haussler
中科院分区：
文献类型：
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作者：
G. Whitfield;J. Hsieh;P. Jurutka;S. Selznick;C. Haussler;P. MacDonald;M. Haussler
最近的研究已经确定了维生素D受体（VDR）和类维生素A X受体（RXR）的异二聚体作为介导1，25-二羟基维生素D3 [1，25（OH）2D3]（维生素D的活性激素形式）的正转录效应的活性复合物。已显示VDR-RXR异二聚体与维生素D靶组织中正调控基因上游的直接重复维生素D应答元件（VDRE）结合，包括骨（骨钙蛋白、骨桥蛋白和β 3整联蛋白）、肾（24-羟化酶）和肠（钙结合蛋白）。通过对VDR突变体的分析，已在C-末端结合结构域中鉴定出参与异源二聚体形成的残基。1，25（OH）2D3配体在VDR-RXR异二聚体转录激活中的作用尚不完全清楚，但对两种天然VDR突变体的研究表明，需要激素和RXR两者的结合来诱导能够激活转录的受体构象。最后一个复杂的水平是最近的观察，VDR被磷酸化修饰。因此，现在已知1，25（OH）2D3的VDR介导的作用涉及多种因素，这些因素可能为未来理解1，25（OH）2D3的组织特异性基因组效应提供概念基础。
Recent studies have identified a heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) as the active complex for mediating positive transcriptional effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active hormonal form of vitamin D. The VDR-RXR heterodimer has been shown to bind to direct repeat vitamin D-responsive elements (VDREs) upstream of positively controlled genes in the target tissues for vitamin D, including bone (osteocalcin, osteopontin, and beta 3 integrin), kidney (24-hydroxylase) and intestine (calbindin). Residues that participate in heterodimer formation have been identified in the C-terminal hormone-binding domain by analysis of VDR mutants. The role of the 1,25(OH)2D3 ligand in transcriptional activation by the VDR-RXR heterodimer is not entirely clear, but studies of two natural VDR mutants suggest that the binding of both hormone and RXR are required to induce a receptor conformation that is competent to activate transcription. A final level of complexity is added by recent observations that VDR is modified by phosphorylation. Thus, the VDR-mediated action of 1,25(OH)2D3 is now known to involve multiple factors that may provide a conceptual basis for future understanding of the tissue-specific genomic effects of 1,25(OH)2D3.