The regulation mechanisms of AhR by molecular chaperone complex

Journal of Biochemistry
Ikuru KudoHideaki Itoh

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...Continue Reading

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Citations

Apr 15, 2020·Journal of Biochemistry·Seiya UemuraHideaki Itoh
Aug 3, 2019·Journal of Experimental & Clinical Cancer Research : CR·Francesca CirilloMarcello Maggiolini
Jun 11, 2019·Oxidative Medicine and Cellular Longevity·Samantha MilanesiDaniela Verzola
Mar 21, 2019·International Journal of Molecular Sciences·Alicia ZamarrónSalvador González
Feb 6, 2019·Nature Reviews. Immunology·Veit Rothhammer, Francisco J Quintana
Apr 8, 2020·International Journal of Molecular Sciences·Anatoly A SoshilovMichael S Denison
Dec 20, 2019·Environmental Science & Technology·Libe Aranguren-AbadíaOdd André Karlsen
Jan 17, 2021·International Journal of Molecular Sciences·Anaïs ParisSébastien Corre
Jan 8, 2021·Cellular & Molecular Immunology·Andreia BarrosoFrancisco J Quintana
Mar 23, 2021·Frontiers in Immunology·Maria Florencia TortiCybele Carina García
Jun 4, 2021·Cellular and Molecular Gastroenterology and Hepatology·Haibo DongZhanxiang Zhou
Jun 14, 2021·Pesticide Biochemistry and Physiology·Yue WangJianhong Li
Oct 9, 2021·Drug Discovery Today·Ting Xiang LimDavid C Reutens

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