SUMOylation is not a prerequisite for HSF1's role in stress protection and transactivation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F25%3A00141596" target="_blank" >RIV/00216224:14310/25:00141596 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41598-025-08735-3" target="_blank" >https://www.nature.com/articles/s41598-025-08735-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-025-08735-3" target="_blank" >10.1038/s41598-025-08735-3</a>

Result language

angličtina

Original language name

SUMOylation is not a prerequisite for HSF1's role in stress protection and transactivation

Original language description

Targeting tumor proteostasis has emerged as a promising strategy in anticancer therapy, particularly through Hsp90 inhibition, which has shown clinical potential. However, the efficacy of Hsp90 inhibitors is limited by the activation of HSF1, a master regulator of the heat shock response (HSR), which mitigates proteotoxic stress by inducing protective chaperones. To address this limitation, we investigated the role of HSF1 SUMOylation in modulating its activity and its impact on Hsp90 inhibitor efficacy. We generated HSF1 mutants with lysine-to-arginine substitutions at five SUMOylation sites and studied their function in H1299 lung carcinoma cells with HSF1/HSF2 knockout, which lack a functional HSR. Unexpectedly, these mutants retained full transcriptional activity during the early phase of the heat shock response, mimicking the initial stress response of wild-type HSF1. SUMOylation inhibition using Subasumstat also led to altered nuclear stress bodies morphology but did not impair Hsp70 induction or enhance Hsp90 inhibitor cytotoxicity. Our findings reveal that SUMOylation is dispensable for HSF1 activation and transactivation capacity during the early phase of HSR. These results refine our understanding of HSF1 regulation and suggest that alternative strategies targeting HSF1 stability and degradation may enhance the therapeutic efficacy of proteostasis-targeting cancer therapies.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Volume of the periodical

15

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

11

Pages from-to

24077

UT code for WoS article

001523084900019

EID of the result in the Scopus database

2-s2.0-105010156472