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Research article 2022 Reviewed

Quantitative Comparison of HSF1 Activators

Christoph Steurer, Sarah Kerschbaum, Christina Wegrostek, Stefan Gabriel, Ali Hallaj, Viktoria Ortner, Thomas Czerny, Elisabeth Riegel

Molecular BiotechnologySpringer Science and Business Media LLC

Abstract via Crossref

Abstract The heat shock response (HSR) pathway is a highly conserved rescue mechanism, which protects the cells from harmful insults disturbing the cellular protein homeostasis via expression of chaperones. Furthermore, it was demonstrated to play crucial roles in various diseases like neurodegeneration and cancer. For neurodegenerative diseases, an overexpression of chaperones is a potential therapeutic approach to clear the cells from non-functional protein aggregates. Therefore, activators of the HSR pathway and its master regulator HSF1 are under close observation. There are numerous HSR activators published in the literature using different model systems, experimental designs, and readout assays. The aim of this work was to provide a quantitative comparison of a broad range of published activators using a newly developed HSF responsive dual-luciferase cell line. Contrary to natural target genes, which are regulated by multiple input pathways, the artificial reporter exclusively reacts to HSF activity. In addition, the results were compared to endogenous heat shock protein expression. As a result, great differences in the intensity of pathway activation were observed. In addition, a parallel viability assessment revealed high variability in the specificity of the drugs. Furthermore, the differences seen compared to published data indicate that some activators exhibit tissue-specific differences leading to interesting assumptions about the regulation of HSF1.

Evidence snapshot note

This reference is cited by the validated MVA · BUB1B evidence snapshot (data as of 2026-10-17) as Steurer et al. — HSF1 reporter evaluation.

Model in the source
Human HSF-responsive reporter and endogenous target systems
Where in the publication
Table 1 and Figure 4: negative arimoclomol response in this system
Cited by evidence records
MVA-ARI-007

The note describes how the snapshot used the source; it is not a summary of the publication's conclusions.

Identifiers and provenance

DOI
10.1007/s12033-022-00467-3
PMID
35218516
PMCID
PMC9259536
Metadata from
Crossref, Europe PMC, OpenAlex, fetched
License (as declared by the source)
https://creativecommons.org/licenses/by/4.0
Open access
Yes
Added
from the MVA evidence snapshot

In the library

Tags
None yet
Keywords from the source
Heat shock response, Neurodegenerative disease, Luciferase assay, Hsf1

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