ArticleMolecular and cellular biology2013
Ubiquitin hydrolase UCH-L1 destabilizes mTOR complex 1 by antagonizing DDB1-CUL4-mediated ubiquitination of raptor.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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.
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Who cites it
53 citing papers in PubMed, 82 citations in OpenAlex.
- The Role of the PI3K/Akt/mTOR Pathway in Atherosclerosis: Mechanisms, Therapeutic Potential, and Emerging Targeted Treatments.Current atherosclerosis reports · 2025Review
- Article
- Post-translational modifications and the reprogramming of tumor metabolism.Discover oncology · 2025Review
- Integrating machine learning for the identification of ubiquitination-associated genes in moyamoya disease.Frontiers in neurology · 2025Article
- USP9X-mediated deubiquitination of Raptor contributes to autophagy impairment and memory deficits in P301S mice.Cell communication and signaling : CCS · 2024Article
- Article
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- Potential roles of UCH family deubiquitinases in tumorigenesis and chemical inhibitors developed against them.American journal of cancer research · 2024Review
- Phosphorylation of OTUB1 at Tyr 26 stabilizes the mTORC1 component, Raptor.Cell death and differentiation · 2023Article
- UCHL1 Promoted Polarization of M1 Macrophages by Regulating the PI3K/AKT Signaling Pathway.Journal of inflammation research · 2022Article
- CD82 protects against glaucomatous axonal transport deficits via mTORC1 activation in mice.Cell death & disease · 2021Article
- Article
- Article
- Deubiquitinases in hematological malignancies.Biomarker research · 2021Review
- VHL suppresses RAPTOR and inhibits mTORC1 signaling in clear cell renal cell carcinoma.Scientific reports · 2021Article
- Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration.Molecular neurodegeneration · 2021Review
- PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling.Nature communications · 2021Article
- Deubiquitinase OTUD5 is a positive regulator of mTORC1 and mTORC2 signaling pathways.Cell death and differentiation · 2021Article
- The Roles of Post-Translational Modifications on mTOR Signaling.International journal of molecular sciences · 2021Review
- Combination Therapy With Rapamycin and Low Dose Imatinib in Pulmonary Hypertension.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates processes including mRNA translation, proliferation, and survival. By assembling with different cofactors, mTOR forms two complexes with distinct biological functions. Raptor-bound mTOR (mTORC1) governs cap-dependent mRNA translation, whereas mTOR, rictor, and mSin1 (mTORC2) activate the survival and proliferative kinase Akt. How the balance between the competing needs for mTORC1 and -2 is controlled in normal cells and deregulated in disease is poorly understood. Here, we show that the ubiquitin hydrolase UCH-L1 regulates the balance of mTOR signaling by disrupting mTORC1. We find that UCH-L1 impairs mTORC1 activity toward S6 kinase and 4EBP1 while increasing mTORC2 activity toward Akt. These effects are directly attributable to a dramatic rearrangement in mTOR complex assembly. UCH-L1 disrupts a complex between the DDB1-CUL4 ubiquitin ligase complex and raptor and counteracts DDB1-CUL4-mediated raptor ubiquitination. These events lead to mTORC1 dissolution and a secondary increase in mTORC2. Experiments in Uchl1-deficient and transgenic mice suggest that the balance between these pathways is important for preventing neurodegeneration and the development of malignancy. These data establish UCH-L1 as a key regulator of the dichotomy between mTORC1 and mTORC2 signaling.
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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.