ArticleNature communications2021
VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 88 citations in OpenAlex.
- Pin1 targets phosphorylated NCOA4 for K29/K48-linked ubiquitination to suppress ferritinophagy and ferroptosis in anaplastic thyroid cancer.Cell death & disease · 2026Article
- SLAP controls mTORC2 integrity via UBE3C-mediated non-degradative mLST8 ubiquitination to suppress colorectal tumorigenesis.Cell death and differentiation · 2026Article
- Deubiquitinases in liver diseases: from mechanisms to targeted therapy.Science China. Life sciences · 2026Review
- K11- and K29-ubiquitination-mediated nuclear translocation of glycolytic enzyme aldolase A promotes pancreatic cancer progression by NF-κB activation.Cell death and differentiation · 2026Article
- Review
- Repeated Exposure to Lidocaine Induces Alzheimer's‐Like Cognitive Impairment and Neuropathology in Aged Mice Through BDNF‐Regulated Autophagy.Journal of cellular and molecular medicine · 2025Article
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- K29-Linked Ubiquitination of Transcription Regulators Controls Cell Proliferation in the Unfolded Protein Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- MINPP1 promotes ferroptosis in HBV-related hepatocellular carcinoma by regulating CTSB K33-linked deubiquitination via ZRANB1.Biology direct · 2025Article
- A depression-associated protein FKBP5 functions in autophagy initiation through scaffolding the VPS34 complex.Molecular neurobiology · 2025Article
- Mitochondrial PTRH2 controls the deubiquitinase TRABID to regulate mt-ND5 stability and metabolism.PNAS nexus · 2025Article
- HACD2 Promotes Pancreatic Cancer Progression by Enhancing PKM2 Dissociation From PRKN in a Dehydratase-Independent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Extracellular Ubiquitin Enhances Autophagy and Inhibits Mitochondrial Apoptosis Pathway to Protect Neurons Against Spinal Cord Ischemic Injury via CXCR4.Neurospine · 2025Article
- OTUD5 Protects Dopaminergic Neurons by Promoting the Degradation of α-Synuclein in Parkinson's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Rapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation.The Journal of cell biology · 2025Article
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- Harnessing miRNA dynamics in HIV-1-infected macrophages: Unveiling new targeted therapeutics using systems biology.Computational and structural biotechnology journal · 2025Article
- Autophagy-based therapy for hepatocellular carcinoma: from standard treatments to combination therapy, oncolytic virotherapy, and targeted nanomedicines.Clinical and experimental medicine · 2024Review
- LncRNA AFAP1-AS1 Promotes Oral Squamous Cell Carcinoma Development by Ubiquitin-Mediated Proteolysis.International dental journal · 2024Article
- UBE3C restricts EV-A71 replication by ubiquitination-dependent degradation of 2C.Journal of virology · 2024Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin-proteasome system (UPS) and autophagy are two major quality control processes whose impairment is linked to a wide variety of diseases. The coordination between UPS and autophagy remains incompletely understood. Here, we show that ubiquitin ligase UBE3C and deubiquitinating enzyme TRABID reciprocally regulate K29/K48-branched ubiquitination of VPS34. We find that this ubiquitination enhances the binding of VPS34 to proteasomes for degradation, thereby suppressing autophagosome formation and maturation. Under ER and proteotoxic stresses, UBE3C recruitment to phagophores is compromised with a concomitant increase of its association with proteasomes. This switch attenuates the action of UBE3C on VPS34, thereby elevating autophagy activity to facilitate proteostasis, ER quality control and cell survival. Specifically in the liver, we show that TRABID-mediated VPS34 stabilization is critical for lipid metabolism and is downregulated during the pathogenesis of steatosis. This study identifies a ubiquitination type on VPS34 and elucidates its cellular fate and physiological functions in proteostasis and liver metabolism.
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