ArticleThe Journal of biological chemistry2019
The RING-type E3 ligase RNF186 ubiquitinates Sestrin-2 and thereby controls nutrient sensing.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- 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
- Potential Role of SESN3 in Linking Heart Failure with Preserved Ejection Fraction and Chronic Obstructive Pulmonary Disease via Autophagy Dysregulation.International journal of molecular sciences · 2025Article
- Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia-Reperfusion Injury Model.Antioxidants (Basel, Switzerland) · 2025Article
- Neuritin affects the activity of neuralized-like 1 by promoting degradation and weakening its affinity for substrate.Acta biochimica et biophysica Sinica · 2023Article
- Review
- Deubiquitinase OTUD5 modulates mTORC1 signaling to promote bladder cancer progression.Cell death & disease · 2022Article
- Cardiac SIRT1 ameliorates doxorubicin-induced cardiotoxicity by targeting sestrin 2.Redox biology · 2022Article
- Deletion of RNF186 expression suppresses diet-induced hepatic steatosis by regulating insulin activity.iScience · 2022Article
- The role of metabolic ecosystem in cancer progression - metabolic plasticity and mTOR hyperactivity in tumor tissues.Cancer metastasis reviews · 2021Review
- Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate receptor-induced unfolded protein response.The Journal of clinical investigation · 2021Article
- The E3 ubiquitin ligase RNF186 andProceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Roles of Post-Translational Modifications on mTOR Signaling.International journal of molecular sciences · 2021Review
- Sestrins in Physiological Stress Responses.Annual review of physiology · 2021Review
- Sestrin2-Mediated Autophagy Contributes to Drug ResistanceFrontiers in cell and developmental biology · 2021Article
- Sestrins: Darkhorse in the regulation of mitochondrial health and metabolism.Molecular biology reports · 2020Review
- The Role of Tissue-Specific Ubiquitin Ligases, RNF183, RNF186, RNF182 and RNF152, in Disease and Biological Function.International journal of molecular sciences · 2020Review
- SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health.Frontiers in cell and developmental biology · 2020Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Nutrient sensing is a critical cellular process controlling metabolism and signaling. mTOR complex 1 (mTORC1) is the primary signaling hub for nutrient sensing and, when activated, stimulates anabolic processes while decreasing autophagic flux. mTORC1 receives nutrient status signals from intracellular amino acid sensors. One of these sensors, Sestrin-2, functions as an intracellular sensor of cytosolic leucine and inhibitor of mTORC1 activity. Genetic studies of Sestrin-2 have confirmed its critical role in regulating mTORC1 activity, especially in the case of leucine starvation. Sestrin-2 is known to be transcriptionally controlled by several mechanisms; however, the post-translational proteolytic regulation of Sestrin-2 remains unclear. Here, we explored how Sestrin-2 is regulated through the ubiquitin proteasome system. Using an unbiased screening approach of an siRNA library targeting ubiquitin E3 ligases, we identified a RING-type E3 ligase, ring finger protein 186 (RNF186), that critically mediates the Sestrin-2 ubiquitination and degradation. We observed that RNF186 and Sestrin-2 bind each other through distinct C-terminal motifs and that Lys-13 in Sestrin-2 is a putative ubiquitin acceptor site. RNF186 knockdown increased Sestrin-2 protein levels and decreased mTORC1 activation. These results reveal a new mechanism of E3 ligase control of mTORC1 activity through the RNF186-Sestrin-2 axis, suggesting that RNF186 inhibition may be a potential strategy to increase levels of the mTORC1 inhibitor Sestrin-2.
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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.