ArticleNature communications2017
The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 110 citations in OpenAlex.
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 2026Article
- Suppression rather than activation of the integrated stress response (GCN2-ATF4) pathway extends lifespan in the fly.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Interplay Between Ribosomal Gene Deficiency and Calorie Restriction in Shaping Yeast Biosynthetic Capacity.Cells · 2025Article
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- Global transcription machinery engineering in Yarrowia lipolytica.FEMS yeast research · 2025Review
- The CDK8 kinase module: A novel player in the transcription of translation initiation and ribosomal genes.Molecular biology of the cell · 2025Article
- A mortality timer based on nucleolar size triggers nucleolar integrity loss and catastrophic genomic instability.Nature aging · 2024Article
- Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells.EMBO reports · 2024Article
- Calorie restriction and rapamycin distinctly restore non-canonical ORF translation in the muscles of aging mice.NPJ Regenerative medicine · 2024Article
- An Interplay between Transcription Factors and Recombinant Protein Synthesis inInternational journal of molecular sciences · 2024Article
- Current limitations in predicting mRNA translation with deep learning models.Genome biology · 2024Article
- Molecular Mechanisms of Genotype-Dependent Lifespan Variation Mediated by Caloric Restriction: Insight from Wild Yeast Isolates.bioRxiv : the preprint server for biology · 2024Article
- Induction of proteasomal activity in mammalian cells by lifespan-extending tRNA synthetase inhibitors.GeroScience · 2024Article
- Molecular mechanisms of genotype-dependent lifespan variation mediated by caloric restriction: insight from wild yeast isolates.Frontiers in aging · 2024Article
- Multiomics ofInternational journal of molecular sciences · 2023Article
- Relationships between Secreted Aspartyl Proteinase 2 and General Control Nonderepressible 4 gene in the Candida albicans resistant to itraconazole under planktonic and biofilm conditions.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Article
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- A comprehensive review and comparison of L-tryptophan biosynthesis inFrontiers in bioengineering and biotechnology · 2023Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Saccharomyces cerevisiae, deletion of large ribosomal subunit protein-encoding genes increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the messenger RNA and protein abundance, ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes, some encoding ribosomal proteins, that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations, including ribosomal protein gene deletions, calorie restriction, and rapamycin treatment, and provide an explanation for its role in longevity and stress response.The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.