TY - JOUR
T1 - Vitamin D receptor (VDR)-mediated actions of 1α,25(OH) 2 vitamin D 3
T2 - Genomic and non-genomic mechanisms
AU - Haussler, Mark R.
AU - Jurutka, Peter
AU - Mizwicki, Mathew
AU - Norman, Anthony W.
N1 - Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2011/8
Y1 - 2011/8
N2 - The conformationally flexible secosteroid, 1α,25(OH) 2 vitamin D 3 (1α,25(OH) 2 D 3 ) initiates biological responses via binding to the vitamin D receptor (VDR). The VDR contains two overlapping ligand binding sites, a genomic pocket (VDR-GP) and an alternative pocket (VDR-AP), that respectively bind a bowl-like ligand configuration (gene transcription) or a planar-like ligand shape (rapid responses). When occupied by 1α,25(OH) 2 D 3 , the VDR-GP interacts with the retinoid X receptor to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1α,25(OH) 2 D 3 . By recruiting complexes of either coactivators or corepressors, activated VDR modulates the transcription of genes encoding proteins that promulgate the traditional genomic functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. 1α,25(OH) 2 D 3 /VDR control of gene expression and rapid responses also delays chronic diseases of aging such as osteoporosis, cancer, type-1 and -2 diabetes, arteriosclerosis, vascular disease, and infection.
AB - The conformationally flexible secosteroid, 1α,25(OH) 2 vitamin D 3 (1α,25(OH) 2 D 3 ) initiates biological responses via binding to the vitamin D receptor (VDR). The VDR contains two overlapping ligand binding sites, a genomic pocket (VDR-GP) and an alternative pocket (VDR-AP), that respectively bind a bowl-like ligand configuration (gene transcription) or a planar-like ligand shape (rapid responses). When occupied by 1α,25(OH) 2 D 3 , the VDR-GP interacts with the retinoid X receptor to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1α,25(OH) 2 D 3 . By recruiting complexes of either coactivators or corepressors, activated VDR modulates the transcription of genes encoding proteins that promulgate the traditional genomic functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. 1α,25(OH) 2 D 3 /VDR control of gene expression and rapid responses also delays chronic diseases of aging such as osteoporosis, cancer, type-1 and -2 diabetes, arteriosclerosis, vascular disease, and infection.
KW - coactivator
KW - corepressor
KW - genomic responses
KW - ligand conformation
KW - rapid responses
KW - retinoid X receptor
KW - transcription
KW - vitamin D receptor
KW - vitamin D responsive elements
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U2 - 10.1016/j.beem.2011.05.010
DO - 10.1016/j.beem.2011.05.010
M3 - Review article
C2 - 21872797
AN - SCOPUS:80052197647
SN - 1521-690X
VL - 25
SP - 543
EP - 559
JO - Best Practice and Research: Clinical Endocrinology and Metabolism
JF - Best Practice and Research: Clinical Endocrinology and Metabolism
IS - 4
ER -