The T-Box near the Zinc Fingers of the Human Vitamin D Receptor Is Required for Heterodimeric DNA Binding and Transactivation

J. C. Hsieh, P. W. Jurutka, S. H. Selznick, M. C. Reeder, C. A. Haussler, G. K. Whitfield, M. R. Haussler

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume215
Issue number1
DOIs
StatePublished - Oct 4 1995

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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