Details
| Original language | English |
|---|---|
| Pages (from-to) | 28932-28945 |
| Number of pages | 14 |
| Journal | ACS Omega |
| Volume | 7 |
| Issue number | 33 |
| Early online date | 9 Aug 2022 |
| Publication status | Published - 23 Aug 2022 |
Abstract
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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In: ACS Omega, Vol. 7, No. 33, 23.08.2022, p. 28932-28945.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Identification of a Thyroid Hormone Binding Site in Hsp90 with Implications for Its Interaction with Thyroid Hormone Receptor Beta
AU - Fan, Lu
AU - Kishore, Anusha
AU - Jansen-Olliges, Linda
AU - Wang, Dahua
AU - Stahl, Frank
AU - Psathaki, Olympia Ekaterini
AU - Harre, Jennifer
AU - Warnecke, Athanasia
AU - Weder, Julia
AU - Preller, Matthias
AU - Zeilinger, Carsten
N1 - Funding Information: L.F. and D.W. were financed by CSC201706180024 and CSC202008080018, respectively; A.K. was funded by the Bundesinstitut für 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).
PY - 2022/8/23
Y1 - 2022/8/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85136260345&partnerID=8YFLogxK
U2 - 10.1021/acsomega.2c02331
DO - 10.1021/acsomega.2c02331
M3 - Article
AN - SCOPUS:85136260345
VL - 7
SP - 28932
EP - 28945
JO - ACS Omega
JF - ACS Omega
IS - 33
ER -