AP-1 and vitamin D receptor (VDR) signaling pathways converge at the rat osteocalcin VDR element: Requirement for the internal activating protein-1 site for vitamin D-mediated trans-activation

Fauzia Aslam, Laura McCabe, Baruch Frenkel, André J. Van Wijnen, Gary S. Stein, Jane B. Lian, Janet L. Stein

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Responsiveness of genes to steroid hormones is a complex process involving synergistic and/or antagonistic interactions between specific receptors and other nonreceptor transcription factors. Thus, DNA recognition elements for steroid hormone receptors are often located among binding sites for other trans-acting factors. The hormonal form of vitamin D, 1,25- dihydroxyvitamin D3, stimulates transcription of the tissue-specific osteocalcin (OC) gene in osteoblastic cells. The rat OC vitamin D response element contains an internal activating protein-1 (AP-1) site. Here, we report for the first time that this AP-1 site is critical for the transcriptional enhancement of rat osteocalcin gene expression mediated by vitamin D. Precise mutations were introduced either in the steroid half- elements or in the internal AP-1 sequences. One mutation within the internal AP-1 site retained vitamin D receptor/retinoid X receptor binding equivalent to that of the wild-type sequence, but resulted in complete loss of vitamin D inducibility of the OC promoter. These results suggest a functional interaction between the hormone receptor and nuclear oncoproteins at the rat OC vitamin D response element. This cooperation of activities may have important consequences in physiological regulation of osteocalcin transcription during osteoblast differentiation and bone tissue development in vivo.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalEndocrinology
Volume140
Issue number1
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Endocrinology

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