論文 - 詳細
| RRC ID | 46154 |
|---|---|
| 著者 | Liu G, Rogers J, Murphy CT, Rongo C. |
| タイトル | EGF signalling activates the ubiquitin proteasome system to modulate C. elegans lifespan. |
| ジャーナル | EMBO J |
| Abstract |
Epidermal growth factor (EGF) signalling regulates growth and differentiation. Here, we examine the function of EGF signalling in Caenorhabditis elegans lifespan. We find that EGF signalling regulates lifespan via the Ras-MAPK pathway and the PLZF transcription factors EOR-1 and EOR-2. As animals enter adulthood, EGF signalling upregulates the expression of genes involved in the ubiquitin proteasome system (UPS), including the Skp1-like protein SKR-5, while downregulating the expression of HSP16-type chaperones. Using reporters for global UPS activity, protein aggregation, and oxidative stress, we find that EGF signalling alters protein homoeostasis in adults by increasing UPS activity and polyubiquitination, while decreasing protein aggregation. We show that SKR-5 and the E3/E4 ligases that comprise the ubiquitin fusion degradation (UFD) complex are required for the increase in UPS activity observed in adults, and that animals that lack SKR-5 or the UFD have reduced lifespans and indications of oxidative stress. We propose that as animals enter fertile adulthood, EGF signalling switches the mechanism for maintaining protein homoeostasis from a chaperone-based approach to an approach involving protein elimination via augmented UPS activity. |
| 巻・号 | 30(15) |
| ページ | 2990-3003 |
| 公開日 | 2011-6-14 |
| DOI | 10.1038/emboj.2011.195 |
| PII | emboj2011195 |
| PMID | 21673654 |
| PMC | PMC3160178 |
| MeSH | Aging / physiology Animals Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Epidermal Growth Factor / metabolism* Kruppel-Like Transcription Factors / metabolism Molecular Chaperones / metabolism Nuclear Proteins / metabolism Proteasome Endopeptidase Complex / metabolism* Signal Transduction* Ubiquitin / metabolism* |
| IF | 9.889 |
| 引用数 | 63 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 6.0 |
| リソース情報 | |
| 線虫 | tm1380 tm544 tm659 |