The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditis elegans
Research output: Contribution to journal › Journal article › Research › peer-review
The general control nonderepressible 2 (GCN2) kinase is a nutrient-sensing pathway that responds to amino acids deficiency and induces a genetic program to effectively maintain cellular homeostasis. Here we established the conserved role of Caenorhabditis elegans GCN-2 under amino acid limitation as a translation initiation factor 2 (eIF2) kinase. Using a combination of genetic and molecular approaches, we showed that GCN-2 kinase activity plays a central role in survival under nutrient stress and mediates lifespan extension conferred by dietary restriction (DR) or inhibition of the major nutrient-sensing pathway, the target of rapamycin (TOR). We also demonstrated that the GCN-2 and TOR signaling pathways converge on the PHA-4/FoxA transcription factor and its downstream target genes to ensure survival of the whole organism under a multitude of stress conditions, such as nutrient scarcity or environmental stresses. This is one step forward in the understanding of evolutionary conserved mechanisms that confer longevity and healthspan.
Original language | English |
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Journal | Aging Cell |
Volume | 12 |
Issue number | 5 |
Pages (from-to) | 742-51 |
Number of pages | 10 |
ISSN | 1474-9718 |
DOIs | |
Publication status | Published - Oct 2013 |
Externally published | Yes |
- Activating Transcription Factors, Amino Acid Sequence, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Eukaryotic Initiation Factor-2, Gene Expression, Longevity, Male, Molecular Sequence Data, Phosphorylation, Protein Kinases, Signal Transduction, Stress, Physiological, TOR Serine-Threonine Kinases
Research areas
ID: 117691643