| Citation | Dubey AA, Sarkar A, Milcz K, Szulc NA, Thapa P, Piechota M, Serwa RA, Pokrzywa W. Floxuridine supports UPS independent of germline signaling and proteostasis regulators via involvement of detoxification in C. elegans. PLoS Genet, 2024. |
| PubMed ID | 39083540 |
| Short Description | Floxuridine supports UPS independent of germline signaling and proteostasis regulators via involvement of detoxification in C. elegans. GEO Record: N.A. Platform: N.A. Download gene-centric, log2 transformed data: WBPaper00067340.ce.ms.csv |
| # of Conditions | 8 |
Full Description
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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. Experimental Details: MassSpec_WBPaper00067340:N2_rep1 MassSpec_WBPaper00067340:N2_rep2 MassSpec_WBPaper00067340:N2_rep3 MassSpec_WBPaper00067340:N2_FUdR_rep1 MassSpec_WBPaper00067340:N2_FUdR_rep2 MassSpec_WBPaper00067340:N2_FUdR_rep3 MassSpec_WBPaper00067340:glp-1(e2144)_rep1 MassSpec_WBPaper00067340:glp-1(e2144)_rep2. |
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