論文 - 詳細
| RRC ID | 46494 |
|---|---|
| 著者 | Segref A, Torres S, Hoppe T. |
| タイトル | A screenable in vivo assay to study proteostasis networks in Caenorhabditis elegans. |
| ジャーナル | Genetics |
| Abstract |
In eukaryotic cells, the ubiquitin/proteasome system (UPS) is a key determinant of proteostasis as it regulates the turnover of damaged proteins. However, it is still unclear how the UPS integrates intrinsic and environmental challenges to promote organismal development and survival. Here, we set up an in vivo degradation assay to facilitate the genetic identification of ubiquitin-dependent proteolysis pathways in the multicellular organism Caenorhabditis elegans. Using this assay, we found that mild induction of protein-folding stress, which is nontoxic for wild-type worms, strongly reduces ubiquitin-dependent protein turnover. Ubiquitin-mediated degradation is also reduced by metabolic stress, which correlates with life-span extension. Unlike other stress conditions, however, acute heat stress results in enhanced rather than reduced proteolysis. Intriguingly, our study provides the first evidence for the existence of tissue-specific degradation requirements because loss of key regulators of the UPS, such as proteasomal subunits, causes accumulation of the model substrate, depending on the tissue type. Thus, here we establish a screenable degradation assay that allows diverse genetic screening approaches for the identification of novel cell-type-specific proteostasis networks important for developmental processes, stress response, and aging, thereby substantially extending the work on recently described mechanistic UPS reporter studies. |
| 巻・号 | 187(4) |
| ページ | 1235-40 |
| 公開日 | 2011-4-1 |
| DOI | 10.1534/genetics.111.126797 |
| PII | genetics.111.126797 |
| PMID | 21288877 |
| PMC | PMC3070531 |
| MeSH | Aging Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Gene Regulatory Networks Genes, Helminth Genome, Helminth Immunoblotting / methods Mutation Proteasome Endopeptidase Complex / genetics Proteasome Endopeptidase Complex / metabolism* Protein Folding Signal Transduction Stress, Physiological Ubiquitin / genetics Ubiquitin / metabolism* |
| IF | 4.015 |
| 引用数 | 28 |
| WOS 分野 | GENETICS & HEREDITY |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 線虫 | tm1380 tm2915 tm1349 tm544 |