| Citation | Thapa P, Chikale RV, Szulc NA, Pandrea MT, Sztyler A, Jaggi K, Niklewicz M, Serwa RA, Hoppe T, Pokrzywa W. HSP70 inhibits CHIP E3 ligase activity to maintain germline function in Caenorhabditis elegans J Biol Chem, 2024. |
| PubMed ID | 39384041 |
| Short Description | HSP70 inhibits CHIP E3 ligase activity to maintain germline function in Caenorhabditis elegans GEO Record: N.A. Platform: N.A. Download gene-centric, log2 transformed data: WBPaper00067432.ce.ms.csv |
| # of Conditions | 16 |
Full Description
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The ubiquitin-proteasome system is crucial for proteostasis, particularly during proteotoxic stress. The interaction between heat shock protein 70 (HSP70) and the ubiquitin ligase CHIP plays a key role in this process. Our study investigates the C. elegans orthologs HSP-1 and CHN-1, demonstrating that HSP-1 binding decreases CHN-1 E3 ligase activity, aligning with the inhibitory effects observed in human HSP70-CHIP interactions. To explore the physiological significance of this inhibition, we utilized the HSP-1EEYD mutant, which binds CHN-1 without reducing its activity, expressed in C. elegans. Our results reveal that the HSP-1-CHN-1 interaction is critical for maintaining germline integrity under heat stress by preventing excessive turnover of essential reproductive proteins. In HSP-1EEYD nematodes, this protective mechanism is impaired, leading to disrupted stress-induced apoptosis, which is restored by CHN-1 depletion. Additionally, proteomic analysis identified DAF-18/PTEN as a potential CHN-1 substrate, which becomes destabilized when CHN-1 activity is not downregulated by HSP-1 during stress. Depleting DAF-18 significantly compromises the reproductive benefits observed from CHN-1 knockout in HSP-1EEYD mutants, suggesting that the maintenance of DAF-18 plays a role in the observed phenotypes. These findings highlight the importance of HSP-1 in regulating CHN-1 E3 ligase activity to preserve germline function under stress conditions. Experimental Details: MassSpec_WBPaper00067432:N2_control_rep1 MassSpec_WBPaper00067432:N2_control_rep2 MassSpec_WBPaper00067432:N2_control_rep3 MassSpec_WBPaper00067432:N2_control_rep4 MassSpec_WBPaper00067432:N2_HeatStress_rep1 MassSpec_WBPaper00067432:N2_HeatStress_rep2 MassSpec_WBPaper00067432:N2_HeatStress_rep3 MassSpec_WBPaper00067432:N2_HeatStress_rep4 MassSpec_WBPaper00067432:hsp-1(syb5159)_control_rep1 MassSpec_WBPaper00067432:hsp-1(syb5159)_control_rep2 MassSpec_WBPaper00067432:hsp-1(syb5159)_control_rep3 MassSpec_WBPaper00067432:hsp-1(syb5159)_control_rep4 MassSpec_WBPaper00067432:hsp-1(syb5159)_HeatStress_rep1 MassSpec_WBPaper00067432:hsp-1(syb5159)_HeatStress_rep2 MassSpec_WBPaper00067432:hsp-1(syb5159)_HeatStress_rep3 MassSpec_WBPaper00067432:hsp-1(syb5159)_HeatStress_rep4. |
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