論文 - 詳細
| RRC ID | 4294 |
|---|---|
| 著者 | Sheaffer KL, Updike DL, Mango SE. |
| タイトル | The Target of Rapamycin pathway antagonizes pha-4/FoxA to control development and aging. |
| ジャーナル | Curr Biol |
| Abstract |
BACKGROUND:FoxA factors are critical regulators of embryonic development and postembryonic life, but little is know about the upstream pathways that modulate their activity. C. elegans pha-4 encodes a FoxA transcription factor that is required to establish the foregut in embryos and to control growth and longevity after birth. We previously identified the AAA+ ATPase homolog ruvb-1 as a potent suppressor of pha-4 mutations. RESULTS:Here we show that ruvb-1 is a component of the Target of Rapamycin (TOR) pathway in C. elegans (CeTOR). Both ruvb-1 and let-363/TOR control nucleolar size and promote localization of box C/D snoRNPs to nucleoli, suggesting a role in rRNA maturation. Inactivation of let-363/TOR or ruvb-1 suppresses the lethality associated with reduced pha-4 activity. The CeTOR pathway controls protein homeostasis and also contributes to adult longevity. We find that pha-4 is required to extend adult lifespan in response to reduced CeTOR signaling. Mutations in the predicted CeTOR target rsks-1/S6 kinase or in ife-2/eIF4E also reduce protein biosynthesis and extend lifespan, but only rsks-1 mutations require pha-4 for adult longevity. In addition, rsks-1, but not ife-2, can suppress the larval lethality associated with pha-4 loss-of-function mutations. CONCLUSIONS:The data suggest that pha-4 and the CeTOR pathway antagonize one another to regulate postembryonic development and adult longevity. We suggest a model in which nutrients promote TOR and S6 kinase signaling, which represses pha-4/FoxA, leading to a shorter lifespan. A similar regulatory hierarchy may function in other animals to modulate metabolism, longevity, or disease. |
| 巻・号 | 18(18) |
| ページ | 1355-64 |
| 公開日 | 2008-9-23 |
| DOI | 10.1016/j.cub.2008.07.097 |
| PII | S0960-9822(08)01118-4 |
| PMID | 18804378 |
| PMC | PMC2615410 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / antagonists & inhibitors* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Larva / physiology Longevity Nuclear Proteins / antagonists & inhibitors Nuclear Proteins / physiology Phenotype Phosphotransferases (Alcohol Group Acceptor) / genetics Phosphotransferases (Alcohol Group Acceptor) / physiology* RNA / genetics RNA Interference Ribonucleoproteins / physiology Trans-Activators / antagonists & inhibitors* Trans-Activators / genetics |
| IF | 9.601 |
| 引用数 | 102 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| 線虫 | tm939 |