ArticleNature communications2015
Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
90 citing papers in PubMed, 148 citations in OpenAlex.
- Leucine Enhances Stress Resistance in Honeybees (Biology · 2026Article
- Interplay Between Sestrin Proteins and Ferroptosis: A Comprehensive Review of Regulatory Mechanisms.Molecular biotechnology · 2026Review
- Doxorubicin induces immediate transcriptional change and apoptosis in spermatogonia from prepubertal rats.Archives of toxicology · 2026Article
- Review
- Paligenosis: dual potential of mature cell plasticity in regeneration and tumorigenesis.MedScience · 2026Review
- Oxidative stress-mediated responses in endometrial cancer cells: contrasting effects of doxorubicin and menadione.Frontiers in physiology · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Allosteric Conformational Locking of Sestrin2 by Leucine: An Integrated Computational Analysis of Branched-Chain Amino Acid Recognition and Specificity.Molecules (Basel, Switzerland) · 2025Article
- Sestrins: a new therapeutic target for endothelial dysfunction and cardiovascular disease prevention.Annals of medicine · 2025Review
- A viral Cyclin D homolog protein hijacks the metabolic stress sensor SESN2 to promote primary effusion lymphoma growth.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Novel Therapeutic Target for Pediatric Pneumonia: Sestrin2.Medicina (Kaunas, Lithuania) · 2025Article
- CSE/HJournal of cachexia, sarcopenia and muscle · 2025Article
- Review
- Article
- Review
- Review
- Review
- Effect of resistance training plus enriched probiotic supplement on sestrin2, oxidative stress, and mitophagy markers in elderly male Wistar rats.Scientific reports · 2024Article
- Sestrin2 ameliorates diabetic retinopathy by regulating autophagy and ferroptosis.Journal of molecular histology · 2024Article
- New insights into GATOR2-dependent interactions and its conformational changes in amino acid sensing.Bioscience reports · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Sestrins are stress-inducible metabolic regulators with two seemingly unrelated but physiologically important functions: reduction of reactive oxygen species (ROS) and inhibition of the mechanistic target of rapamycin complex 1 (mTORC1). How Sestrins fulfil this dual role has remained elusive so far. Here we report the crystal structure of human Sestrin2 (hSesn2), and show that hSesn2 is twofold pseudo-symmetric with two globular subdomains, which are structurally similar but functionally distinct from each other. While the N-terminal domain (Sesn-A) reduces alkylhydroperoxide radicals through its helix-turn-helix oxidoreductase motif, the C-terminal domain (Sesn-C) modified this motif to accommodate physical interaction with GATOR2 and subsequent inhibition of mTORC1. These findings clarify the molecular mechanism of how Sestrins can attenuate degenerative processes such as aging and diabetes by acting as a simultaneous inhibitor of ROS accumulation and mTORC1 activation.
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Registered trials
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.