Introduction
However, occasionally unwanted immune reactions against self-tissue that lead to autoimmune diseases occur. Low serum levels of 25(OH)D 3 have also been linked to higher susceptibility to infections such as tuberculosis (Nnoaham and Clarke, 2008), influenza (Cannell et al., 2006; Grant, 2008), HIV (Rodriguez et al., 2009), respiratory syncytial virus (Grant, 2008), and viral infections of the upper respiratory tract (Ginde et al., 2009). It is therefore apparent that vitamin D plays a role in immune modulation.
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Omodimerization vs. Heterodimerization
VDR functions as a heterodimer with RXR for activation of gene transcription. However, a few studies ndicated that purified VDR can bind as a homodimer to certain VDREs but that RXR was required for binding to other VDREs (Freedman et al., 1994; Nishikawa et al., 1994). 9-cis-Retinoic acid has been reported to decrease heterodimer formation by driving the equilibrium from the VDR heterodimer to the RXR homodimer or to the interaction of RXR with other receptors (Cheskis and Freedman, 1994; MacDonald et al., 1993).
Regions of VDR within the ligand-binding domain (LBD) that may be crucial for heterodimerization have been suggested. Mutagenesis studies have indicated that the regions in the C-terminal between amino acids 317 and 395 and between amino acids 244 and 263 corresponding to portions of helices 7–10 and 3–4, respectively, are important for ligand dependent heterodimerization (Nakajima et al., 1994; Jin et al., 1996; Rosen et al., 1993; Whitfield et al., 1995). A more complete understanding of the three-dimensional contacts between VDR and RXR and between VDR and other accessory factors will be obtained now that the crystal structure of the VDR ligand domain bound to its ligand has been published (Rochel et al., .
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Ety of biological actions such as calcium homeostasis, cell proliferation and cell differentiation to many target tissues. Most of these biological actions of vitamin D are now considered to be exerted through the nuclear vitamin D receptor (VDR)-mediated control of target genes. The function of VDR as a ligand-induced transcription factor is overviewed, and the phenotype of VDR gene knock-out mice and the VDR-mediated transcriptional and negative regulation of the key enzyme in vitamin D biosynthesis are also described, based mainly on our recent findings, to gain a better understanding of the function of VDR in the transcriptional control of vitamin D target gene.