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

Jui-Cheng Hsieh, P. W. Jurutka, S. H. Selznick, M. C. Reeder, C. A. Haussler, G Kerr Whitfield, Mark R Haussler

Research output: Contribution to journalArticle

28 Citations (Scopus)

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

Fingerprint

Calcitriol Receptors
Zinc Fingers
Transcriptional Activation
Retinoid X Receptors
Zinc
Chemical activation
Glucocorticoid Receptors
Vitamin D
lysylglutamic acid
DNA
Steroid hormones
Steroid Receptors
Osteocalcin
Rats
Hormones
Amino Acids

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Biophysics
  • Biochemistry

Cite this

The T-Box near the Zinc Fingers of the Human Vitamin D Receptor Is Required for Heterodimeric DNA Binding and Transactivation. / Hsieh, Jui-Cheng; Jurutka, P. W.; Selznick, S. H.; Reeder, M. C.; Haussler, C. A.; Whitfield, G Kerr; Haussler, Mark R.

In: Biochemical and Biophysical Research Communications, Vol. 215, No. 1, 04.10.1995, p. 1-7.

Research output: Contribution to journalArticle

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