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Identification of a Thyroid Hormone Binding Site in Hsp90 with Implications for Its Interaction with Thyroid Hormone Receptor Beta

  • While many proteins are known clients of heat shock protein 90 (Hsp90), it is unclear whether the transcription factor, thyroid hormone receptor beta (TRb), interacts with Hsp90 to control hormonal perception and signaling. Higher Hsp90 expression in mouse fibroblasts was elicited by the addition of triiodothyronine (T3). T3 bound to Hsp90 and enhanced adenosine triphosphate (ATP) binding of Hsp90 due to a specific binding site for T3, as identified by molecular docking experiments. The binding of TRb to Hsp90 was prevented by T3 or by the thyroid mimetic sobetirome. Purified recombinant TRb trapped Hsp90 from cell lysate or purified Hsp90 in pull-down experiments. The affinity of Hsp90 for TRb was 124 nM. Furthermore, T3 induced the release of bound TRb from Hsp90, which was shown by streptavidin-conjugated quantum dot (SAv-QD) masking assay. The data indicate that the T3 interaction with TRb and Hsp90 may be an amplifier of the cellular stress response by blocking Hsp90 activity.

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Document Type:Article
Author:Lu Fan, Anusha Kishore, Linda Jansen-Olliges, Dahua Wang, Frank Stahl, Olympia Ekaterini Psathaki, Jennifer Harre, Athanasia Warnecke, Julia Weder, Matthias Preller, Carsten Zeilinger
Parent Title (English):ACS Omega
Number of pages:14
First Page:28932
Last Page:28945
Publisher:American Chemical Society (ACS)
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2022/08/09
Copyright:Copyright © 2022 The Authors. Published by American Chemical Society.
Funding:L.F. and D.W. were financed by CSC201706180024 and CSC202008080018, respectively; A.K. was funded by the Bundesinstitut fur Sportwissenschaft (BISP, ZMVI4-070514/ 20-21) and E.P. by the DFG SFB 944 Z-Project. The DFG FOR Cytolabs also supported consumables, Excellence Cluster Rebirth Innovation-/Synergy Grants Screening of Telomerase Stimulators for Cardiac Regeneration & Repair (CR&R) by Cell Microarrays and the Cluster of Excellence Hearing4All (EXC 2177/1).
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Institut für Technik, Ressourcenschonung und Energieeffizienz (TREE)
Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Entry in this database:2022/09/02
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International