ArticlePLoS genetics2014
The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to protein N-terminal acetylation.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 44 citations in OpenAlex.
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- Illuminating the impact of N-terminal acetylation: from protein to physiology.Nature communications · 2025Review
- GOA-1 regulates spermathecal transits.microPublication biology · 2025Article
- N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity.Nature communications · 2023Article
- Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development.Scientific reports · 2022Article
- Host Immunity Alters Community Ecology and Stability of the Microbiome in a Caenorhabditis elegans Model.mSystems · 2021Article
- Human NAA30 can rescue yeast mak3∆ mutant growth phenotypes.Bioscience reports · 2021Article
- The Function ofInsects · 2020Article
- Natural variation in the sequestosome-related gene, sqst-5, underlies zinc homeostasis in Caenorhabditis elegans.PLoS genetics · 2020Article
- Short-Term Mild Temperature-Stress-Induced Alterations in theInternational journal of molecular sciences · 2020Article
- Chinese liquor extract attenuates oxidative damage in HepG2 cells and extends lifespan ofFood science & nutrition · 2020Article
- A Dihydroflavonoid Naringin Extends the Lifespan ofOxidative medicine and cellular longevity · 2020Article
- DAF-16/FOXO promotes taste avoidance learning independently of axonal insulin-like signaling.PLoS genetics · 2019Article
- N-terminal Acetylation Levels Are Maintained During Acetyl-CoA Deficiency inMolecular & cellular proteomics : MCP · 2018Article
- Role of Caenorhabditis elegans AKT-1/2 and SGK-1 in Manganese Toxicity.Neurotoxicity research · 2018Article
- A pathway for low zinc homeostasis that is conserved in animals and acts in parallel to the pathway for high zinc homeostasis.Nucleic acids research · 2017Article
- The Nuclear Receptor HIZR-1 Uses Zinc as a Ligand to Mediate Homeostasis in Response to High Zinc.PLoS biology · 2017Article
- A Role for Human N-alpha Acetyltransferase 30 (Naa30) in Maintaining Mitochondrial Integrity.Molecular & cellular proteomics : MCP · 2016Article
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9 authors at 2 institutions in 1 country.
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Abstract
The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT) complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance.
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