The regulation mechanisms of AhR by molecular chaperone complex

Ikuru Kudo, Miki Hosaka, Asami Haga, Noriko Tsuji, Yuhtaroh Nagata, Hirotaka Okada, Kana Fukuda, Yuka Kakizaki, Tomoya Okamoto, Ewa Grave, Hideaki Itoh

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The AhR, so called the dioxin receptor, is a member of the nuclear receptor superfamily. The ligand-free AhR forms a cytosolic protein complex with the molecular chaperone HSP90, co-chaperone p23, and XAP2 in the cytoplasm. Following ligand binding like 2, 3, 7, 8-tetrachlorodibenzo- p-dioxin (TCDD), the AhR translocates into the nucleus. Although it has been reported that HSP90 regulates the translocation of the AhR to the nucleus, the precise activation mechanisms of the AhR have not yet been fully understood. AhR consists of the N-terminal bHLH domain containing NLS and NES, the middle PAS domain and the C-terminal transactivation domain. The PAS domain is familiar as a ligand and HSP90 binding domain. In this study, we focused on the bHLH domain that was thought to be a HSP90 binding domain. We investigated the binding properties of bHLH to HSP90. We analyzed the direct interaction of bHLH with HSP90, p23 and XAP2 using purified proteins. We found that not only the PAS domain but also the bHLH domain bound to HSP90. The bHLH domain forms complex with HSP90, p23 and XAP2. We also determined the bHLH binding domain was HSP90 N-domain. The bHLH domain makes a complex with HSP90, p23 and XAP2 via the HSP90 N-domain. Although the NLS is closed in the absence of a ligand, the structure of AhR will be changed in the presence of a ligand, which leads to NLS open, result in the nuclear translocation of AhR.

Original languageEnglish
Pages (from-to)223-232
Number of pages10
JournalJournal of Biochemistry
Volume163
Issue number3
DOIs
Publication statusPublished - Mar 1 2018
Externally publishedYes

Keywords

  • AhR
  • aryl hydrocarbon receptor
  • co-chaperone
  • HSP90
  • molecular chaperone

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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  • Cite this

    Kudo, I., Hosaka, M., Haga, A., Tsuji, N., Nagata, Y., Okada, H., Fukuda, K., Kakizaki, Y., Okamoto, T., Grave, E., & Itoh, H. (2018). The regulation mechanisms of AhR by molecular chaperone complex. Journal of Biochemistry, 163(3), 223-232. https://doi.org/10.1093/jb/mvx074