Issa L L, Leong G M, Eisman J A
Bone and Mineral Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, NSW, Australia.
Inflamm Res. 1998 Dec;47(12):451-75. doi: 10.1007/s000110050360.
The vitamin D system is unique in that distinct calcium homeostatic functions and cell growth regulatory activities are mediated through a single ligand, calcitriol, acting through a specific receptor exhibiting ubiquitous tissue expression, the vitamin D receptor (VDR). The VDR is a member of a superfamily of nuclear steroid hormone receptors which regulate gene transcription by interacting with response elements in gene promoters. Structure-function analysis of the VDR protein has defined distinct domains involved in DNA binding, ligand binding, receptor dimerisation and gene transactivation, including a C-terminal activation function domain (AF-2) that is important for cofactor interaction. A model for regulation of gene transcription by the VDR is evolving and proposes VDR interaction with various components of the basal transcriptional machinery, including newly defined coactivators and corepressors, which may act to regulate gene transcription by altering histone acetylation and chromatin structure. This review describes the vitamin D endocrine system and the role of the VDR in regulating this system, including the molecular basis for the diverse actions of synthetic calcitriol analogues in the treatment of autoimmune disease and cancer.
维生素D系统独具特色，在于其独特的钙稳态功能和细胞生长调节活性是通过单一配体骨化三醇介导的，骨化三醇通过一种在组织中广泛表达的特异性受体——维生素D受体（VDR）发挥作用。VDR是核类固醇激素受体超家族的成员之一，通过与基因启动子中的反应元件相互作用来调节基因转录。对VDR蛋白的结构-功能分析确定了参与DNA结合、配体结合、受体二聚化和基因反式激活的不同结构域，包括对辅因子相互作用很重要的C端激活功能域（AF-2）。VDR调节基因转录的模型正在不断发展，该模型提出VDR与基础转录机制的各种组分相互作用，包括新定义的共激活因子和共抑制因子，它们可能通过改变组蛋白乙酰化和染色质结构来调节基因转录。本文综述了维生素D内分泌系统以及VDR在调节该系统中的作用，包括合成骨化三醇类似物在治疗自身免疫性疾病和癌症中多种作用的分子基础。
