論文 - 詳細
| RRC ID | 53342 |
|---|---|
| 著者 | Ferraz RC, Camara H, De-Souza EA, Pinto S, Pinca AP, Silva RC, Sato VN, Castilho BA, Mori MA. |
| タイトル | IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans. |
| ジャーナル | BMC Biol |
| Abstract |
BACKGROUND:The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2. RESULTS:Here, we tested whether IMPACT down-regulation mimics the effects of DR in C. elegans. Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2-dependent manner. Impt-1 knockdown exacerbated DR-induced longevity and required several DR-activated transcription factors to extend lifespan, among them SKN-1 and DAF-16, which were induced during larval development and adulthood, respectively, in response to impt-1 RNAi. CONCLUSIONS:IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR. |
| 巻・号 | 14(1) |
| ページ | 87 |
| 公開日 | 2016-10-7 |
| DOI | 10.1186/s12915-016-0301-2 |
| PII | 10.1186/s12915-016-0301-2 |
| PMID | 27717342 |
| PMC | PMC5054600 |
| MeSH | Animals Caenorhabditis elegans / drug effects* Caenorhabditis elegans / enzymology* Caenorhabditis elegans Proteins / antagonists & inhibitors* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Protein Kinase Inhibitors / pharmacology* Protein Kinases / genetics Protein Kinases / metabolism* RNA Interference Signal Transduction / genetics Signal Transduction / physiology Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 6.765 |
| 引用数 | 8 |
| リソース情報 | |
| 線虫 | tm4397 |