Abstract
Our laboratories have been interested in the mechanism by which steroid receptors in general, and the 1,25-dihydroxyvitamin D (1,25(0H)2D) receptor specifically, interact with sequences in the target cell genome and regulate the transcription of specific gene products. Elucidation of these structure-function relationships of the l,25-(OH)2D3 receptor macromolecule have been hampered primarily because of its extremely low intracellular concentration (0.001%), even in primary target tissues such as intestine. This concentration is less than onetenth the cellular concentration of other steroid receptor molecules. Nonetheless, Pike and Haussler succeeded in purifying the chicken intestinal vitamin D receptor (1) and raised monoclonal antibodies which were reactive to both the chicken and mammalian isoforms (2). The monoclonals were used to recover vitamin D receptor (VDR) complementary DNA (cDNA) from a chicken intestine expression library (3). Subsequently, the chicken clones were used as probes to screen several human cDNA libraries and isolate the mammalian full length cDNA encoding the VDR (4). The nucleotide sequence of the 4605 base pair human cDNA was shown to include 1281 bp of open reading frame, 115 bp of noncoding leader sequence, and 3209 bp of 3′- noncoding sequence. The cloned sequence was subsequently transfected into COS-1 receptor negative monkey kidney cells and a single VDR species was produced that was indistinguishable from the native receptor (4).
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References
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© 1989 Plenum Press, New York
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Hughes, M. et al. (1989). Human Vitamin D Receptor Mutations: Identification of Molecular Defects in Hypocalcemic Vitamin D Resistant Rickets. In: Hidaka, H., Carafoli, E., Means, A.R., Tanaka, T. (eds) Calcium Protein Signaling. Advances in Experimental Medicine and Biology, vol 255. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5679-0_52
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