PMID- 7575575 OWN - NLM STAT- MEDLINE DCOM- 19951109 LR - 20081121 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 215 IP - 1 DP - 1995 Oct 4 TI - The T-box near the zinc fingers of the human vitamin D receptor is required for heterodimeric DNA binding and transactivation. PG - 1-7 AB - The T-box mediates binding of retinoid X receptor (RXR) homodimers to DNA while the P- and D-box in the zinc fingers of steroid hormone receptors play roles in DNA-binding specificity and homodimerization, respectively. We investigated the function of these elements in the human vitamin D receptor (hVDR) by mutating a Lys-Glu pair of amino acids in the T-box, and by altering the P- and D-boxes to the corresponding residues of the glucocorticoid receptor (GR). The T-box mutant hVDR displayed attenuated vitamin D responsive element (VDRE) binding in the presence of RXR and was severely compromised in transcriptional activation. In contrast, GR P/D-box mutant hVDRs bound to the rat osteocalcin VDRE and elicited near normal transcriptional activation. The T-box mutant uniquely exhibited dominant negative properties, highlighting the significance of this region of hVDR for heterodimeric transcriptional activation. FAU - Hsieh, J C AU - Hsieh JC AD - Department of Biochemistry, College of Medicine, University of Arizona, Tucson 85724, USA. FAU - Jurutka, P W AU - Jurutka PW FAU - Selznick, S H AU - Selznick SH FAU - Reeder, M C AU - Reeder MC FAU - Haussler, C A AU - Haussler CA FAU - Whitfield, G K AU - Whitfield GK FAU - Haussler, M R AU - Haussler MR LA - eng GR - AR-15781/AR/NIAMS NIH HHS/United States GR - DK-33351/DK/NIDDK NIH HHS/United States GR - DK49604-01/DK/NIDDK NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Macromolecular Substances) RN - 0 (Receptors, Calcitriol) RN - 9007-49-2 (DNA) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cell Line MH - DNA/*metabolism MH - Humans MH - Macromolecular Substances MH - Molecular Sequence Data MH - Mutagenesis, Site-Directed MH - Rats MH - Receptors, Calcitriol/*chemistry/genetics/*metabolism MH - Structure-Activity Relationship MH - *Transcriptional Activation MH - Transfection MH - *Zinc Fingers EDAT- 1995/10/04 00:00 MHDA- 1995/10/04 00:01 CRDT- 1995/10/04 00:00 PHST- 1995/10/04 00:00 [pubmed] PHST- 1995/10/04 00:01 [medline] PHST- 1995/10/04 00:00 [entrez] AID - S0006-291X(85)72426-6 [pii] AID - 10.1006/bbrc.1995.2426 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1995 Oct 4;215(1):1-7. doi: 10.1006/bbrc.1995.2426.