New mechanisms of regulation of the genomic actions of vitamin D in bone cells: interaction of the vitamin D receptor with non-classical response elements and with the multifunctional protein, calreticulin.
Vitamin D exerts its genomic effects following binding to a specific receptor which is a member of the steroid hormone receptor superfamily. The vitamin D receptor (VDR) forms heterodimers with retinoid X receptors (RXRs) and the dimer then interacts with its cognate binding site, termed vitamin D response element (VDRE), to affect the transcription of target genes. Recent studies have identified novel sequence motifs for VDREs as well as novel protein-protein interactions involving the VDR. These will be reviewed with particular emphasis on the complex VDRE from the c-fos proto-oncogene promoter region and the inhibition of the vitamin D signal transduction pathway by the multifunctional protein, calreticulin. Thus research on the control of gene transcription by vitamin D reveals examples of molecular interplay between transcriptional regulatory pathways and provides new insight into the molecular mechanism of action of vitamin D.
St-Arnaud
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Genetics Unit, Shriners Hospital, and Department of Surgery, McGill University, Montréal, Québec, Canada H3G1A6. arnaud@shiners.mcgill.ca
Candeliere
G A
GA
Dedhar
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S
D001483:Base Sequence; D001665:Binding Sites; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology*; D002117:Calcitriol / Q000502:physiology; D037282:Calreticulin / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D018167:Receptors, Calcitriol / Q000235:genetics / Q000502:physiology*; D014807:Vitamin D / Q000502:physiology*
D037282:Calreticulin; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D018167:Receptors, Calcitriol; D014807:Vitamin D; D002117:Calcitriol