論文 - 詳細
| RRC ID | 84092 |
|---|---|
| 著者 | Thapa P, Chikale RV, Szulc NA, Pandrea MT, Sztyler A, Jaggi K, Niklewicz M, Serwa RA, Hoppe T, Pokrzywa W. |
| タイトル | HSP70 inhibits CHIP E3 ligase activity to maintain germline function in Caenorhabditis elegans. |
| ジャーナル | J Biol Chem |
| Abstract |
The ubiquitin-proteasome system is crucial for proteostasis, particularly during proteotoxic stress. The interaction between heat shock protein (HSP) 70 and the ubiquitin ligase CHIP plays a key role in this process. Our study investigates the Caenorhabditis 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. |
| 巻・号 | 300(11) |
| ページ | 107864 |
| 公開日 | 2024-11-1 |
| DOI | 10.1016/j.jbc.2024.107864 |
| PII | S0021-9258(24)02366-4 |
| PMID | 39384041 |
| PMC | PMC11567022 |
| MeSH | Animals Apoptosis Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Germ Cells* / metabolism HSP70 Heat-Shock Proteins* / genetics HSP70 Heat-Shock Proteins* / metabolism Heat-Shock Response / physiology Ubiquitin-Protein Ligases* / genetics Ubiquitin-Protein Ligases* / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 11 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm6709 tm1759 tm5921 tm6321 tm10273 tm2664 tm662 |