Floxuridine supports UPS independent of germline signaling and proteostasis regulators via involvement of detoxification in C. elegans.
PLoS Genet
; 20(7): e1011371, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-39083540
ABSTRACT
The ubiquitin-proteasome system (UPS) is critical for maintaining proteostasis, influencing stress resilience, lifespan, and thermal adaptability in organisms. In Caenorhabditis elegans, specific proteasome subunits and activators, such as RPN-6, PBS-6, and PSME-3, are associated with heat resistance, survival at cold (4°C), and enhanced longevity at moderate temperatures (15°C). Previously linked to improving proteostasis, we investigated the impact of sterility-inducing floxuridine (FUdR) on UPS functionality under proteasome dysfunction and its potential to improve cold survival. Our findings reveal that FUdR significantly enhances UPS activity and resilience during proteasome inhibition or subunit deficiency, supporting worms' normal lifespan and adaptation to cold. Importantly, FUdR effect on UPS activity occurs independently of major proteostasis regulators and does not rely on the germ cells proliferation or spermatogenesis. Instead, FUdR activates a distinct detoxification pathway that supports UPS function, with GST-24 appearing to be one of the factors contributing to the enhanced activity of the UPS upon knockdown of the SKN-1-mediated proteasome surveillance pathway. Our study highlights FUdR unique role in the UPS modulation and its crucial contribution to enhancing survival under low-temperature stress, providing new insights into its mechanisms of action and potential therapeutic applications.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
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Caenorhabditis elegans
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Floxuridine
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Caenorhabditis elegans Proteins
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Ubiquitin
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Proteasome Endopeptidase Complex
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Proteostasis
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Germ Cells
Limits:
Animals
Language:
En
Journal:
PLoS Genet
Journal subject:
GENETICA
Year:
2024
Document type:
Article
Affiliation country:
Poland
Country of publication:
United States