The specific DNA binding activity of the dioxin receptor is modulated by the 90kd heat shock protein

A. Wilhelmsson, S. Cuthill, M. Denis, A. C. Wikstrom, J. A. Gustafsson, L. Poellinger

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

Abstract

The dioxin receptor is a gene regulatory protein which exhibits many structural and functional similarities to steroid hormone receptors. In this study we compare the subunit composition of two forms of the dioxin receptor, sedimenting at ∼9S and ∼6S respectively, which are present in nuclear extract from wild-type Hepa 1c1c7 mouse hepatoma cells following treatment in vivo with dioxin. The nuclear ∼9S receptor form contained the 90 kd heat shock protein, hsp90. As assessed by a gel mobility shift assay, this receptor form did not bind to the xenobiotic response element (XRE) of the target gene cytochrome P-450 IA1. In contrast, the smaller ∼6S receptor form did not contain any immunochemically detectable hsp90. Moreover, this receptor form specifically bound to the XRE recognition sequence. Thus, the specific DNA binding activity of the dioxin receptor was inhibited by association with hsp90, and the ∼9S dioxin receptor species could be regarded as a nonactive receptor form. Neither the ∼9S nor the ∼6S receptor forms were detected in nuclear extract from a dioxin treated mutant done of Hepa 1 that expresses a nuclear translocation deficient receptor phenotype. We conclude that activation of the dioxin receptor is, at least, a two step process involving binding of the ligand and dissociation of hsp90 from the ligand-binding receptor protein. Inhibition of the DNA binding activity of transcription factors by protein-protein interaction has also been described for several steroid hormone receptors and for the NFxB factor. Finally, the presence of hsp90 in the nuclear extract suggests that hsp90 may play a role in modulation of the DNA binding activity of the receptor within the nucleus.

Original languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalEMBO Journal
Volume9
Issue number1
DOIs
StatePublished - 1990

Keywords

  • Dioxin receptor
  • Hsp90
  • Protein - DNA interaction
  • Protein-protein interaction
  • Transcription factors

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'The specific DNA binding activity of the dioxin receptor is modulated by the 90kd heat shock protein'. Together they form a unique fingerprint.

Cite this