ArticleCell death and differentiation2021
Deubiquitinase OTUD5 is a positive regulator of mTORC1 and mTORC2 signaling pathways.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Rewiring KRAS-driven cancers through the ubiquitin-proteasome system: therapeutic opportunities with a focus on deubiquitinase.Experimental & molecular medicine · 2026Review
- OTUD5-TIF1γ-SMAD3/4 positive feedback loop inhibits TGF-β-induced EMT and metastasis in NSCLC.Cell death & disease · 2026Article
- OTUD5-related rare X-linked multiple congenital anomalies and neurodevelopmental syndrome: clinical findings and review of the literature.Neurogenetics · 2026Review
- Proteasome activity maintains cell-type-specific gene expression.Cell reports · 2026Article
- OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026Review
- OTU deubiquitinases as immune-circuit editors: from human immunopathology to therapeutic prioritization.Frontiers in immunology · 2026Review
- Entrectinib binds to HMGB1 and activates cardiomyocyte autophagy by inhibiting OTUD5-MTORC1 signaling to induce cardiotoxicity.Autophagy · 2025Article
- Ubiquitination in the Nervous System: From Molecular Mechanisms to Disease Implications.Molecular neurobiology · 2025Review
- DUBA sustains the stability of NOD2 and RIPK2 to enhance innate immune responses.Cell death and differentiation · 2025Article
- OTUD5 Protects Dopaminergic Neurons by Promoting the Degradation of α-Synuclein in Parkinson's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- OTUD5 promotes end-joining of deprotected telomeres by promoting ATM-dependent phosphorylation of KAP1Nature communications · 2024Article
- Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response.The EMBO journal · 2024Article
- Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival.Cell death & disease · 2024Article
- OTUD5 promotes the inflammatory immune response by enhancing MyD88 oligomerization and Myddosome formation.Cell death and differentiation · 2024Article
- OTUD5 promotes the growth of hepatocellular carcinoma by deubiquitinating and stabilizing SLC38A1.Biology direct · 2024Article
- Review
- Autophagy of OTUD5 destabilizes GPX4 to confer ferroptosis-dependent kidney injury.Nature communications · 2023Article
- Deubiquitinases in cancer.Nature reviews. Cancer · 2023Review
- Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian Target of Rapamycin (mTOR) pathway regulates a variety of physiological processes, including cell growth and cancer progression. The regulatory mechanisms of these signals are extremely complex and comprise many feedback loops. Here, we identified the deubiquitinating enzyme ovarian tumor domain-containing protein 5 (OTUD5) as a novel positive regulator of the mTOR complex (mTORC) 1 and 2 signaling pathways. We demonstrated that OTUD5 stabilized β-transducin repeat-containing protein 1 (βTrCP1) proteins via its deubiquitinase (DUB) activity, leading to the degradation of Disheveled, Egl-10, and pleckstrin domain-containing mTOR-interacting protein (DEPTOR), which is an inhibitory protein of mTORC1 and 2. We also showed that mTOR directly phosphorylated OTUD5 and activated its DUB activity. RNA sequencing analysis revealed that OTUD5 regulates the downstream gene expression of mTOR. Additionally, OTUD5 depletion elicited several mTOR-related phenotypes such as decreased cell size and increased autophagy in mammalian cells as well as the suppression of a dRheb-induced curled wing phenotype by RNA interference of Duba, a fly ortholog of OTUD5, in Drosophila melanogaster. Furthermore, OTUD5 knockdown inhibited the proliferation of the cancer cell lines with mutations activating mTOR pathway. Our results suggested a positive feedback loop between OTUD5 and mTOR signaling pathway.
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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.