論文 - 詳細
| RRC ID | 45699 |
|---|---|
| 著者 | Carrano AC, Dillin A, Hunter T. |
| タイトル | A Krüppel-like factor downstream of the E3 ligase WWP-1 mediates dietary-restriction-induced longevity in Caenorhabditis elegans. |
| ジャーナル | Nat Commun |
| Abstract |
The HECT ubiquitin E3 ligase WWP-1 is a positive regulator of lifespan in response to dietary restriction (DR) in Caenorhabditis elegans. However, substrates of WWP-1 for ubiquitylation in the DR pathway have not yet been identified. Here we identify the C. elegans Krüppel-like factor, KLF-1, as an essential and specific regulator of DR-induced longevity and a substrate for ubiquitylation by WWP-1. Knockdown of klf-1 suppresses the extended lifespan of both DR animals and wwp-1-overexpressing animals, indicating that KLF-1 functions within the same pathway as WWP-1. In addition, overexpression of klf-1 in the intestine is sufficient to extend the lifespan of WT animals on an ad libitum diet, and requires wwp-1 or pha-4/FoxA. We demonstrate that WWP-1 directly interacts with KLF-1 and mediates multiple monoubiquitylation of KLF-1 in vitro and in cellulo. Our data support a model in which modulation of KLF-1 by WWP-1 regulates diet-restriction-induced longevity. |
| 巻・号 | 5 |
| ページ | 3772 |
| 公開日 | 2014-5-8 |
| DOI | 10.1038/ncomms4772 |
| PII | ncomms4772 |
| PMID | 24805825 |
| PMC | PMC4346368 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / biosynthesis Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Caloric Restriction* Diet / methods Intestinal Mucosa / metabolism Kruppel-Like Transcription Factors / biosynthesis Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism* Longevity / genetics RNA Interference RNA, Small Interfering Trans-Activators / metabolism Ubiquitin-Protein Ligases / biosynthesis Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* Ubiquitination |
| IF | 12.121 |
| 引用数 | 13 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| 線虫 | tm731 tm1110 |