ArticleAutophagy2024
USP20 deubiquitinates and stabilizes the reticulophagy receptor RETREG1/FAM134B to drive reticulophagy.
Article in Autophagy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- A USP28-TM9SF3-Golgiphagy axis maintains glycosylation homeostasis and promotes breast cancer progression.The EMBO journal · 2026Article
- The role of ubiquitin system in ageing-related diseases and potential therapeutic opportunities.Molecular biomedicine · 2026Review
- Targeting VAMPs in Aging-Related Diseases: From Mechanisms to Pharmacotherapy.Pharmaceutical research · 2026Review
- ER-phagy receptors: structural mechanisms in selective ER degradation and disease implications.Acta pharmacologica Sinica · 2026Review
- USP33 alleviates FIS1-dependent mitochondrial fission and cardiac microvascular injury in diabetic cardiomyopathy via deubiquitinating and stabilizing ATG7.Cell death & disease · 2026Article
- Post-translational modifications of selective autophagy receptors: orchestrating cellular homeostasis, disease pathogenesis, and therapeutic opportunities.Cellular & molecular biology letters · 2026Review
- Cardiomyocyte-Derived USP20 Attenuates Diabetic Cardiomyopathy by Facilitating the Degradation of STING and Mitigating STING-Mediated Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The multiple roles of Ggt1-Cre in the generation of transgenic mice.Cellular & molecular biology letters · 2026Article
- Icariin-mediated structural stabilization of TNF-α triggers a pro-regenerative signaling switch for endothelial recovery after myocardial infarction.Frontiers in pharmacology · 2026Article
- Cardiomyocyte-derived USP20 mitigates myocardial ischemia/reperfusion injury through deubiquitinating GRP78.Theranostics · 2026Article
- Endoplasmic reticulum autophagy in inflammatory diseases.Frontiers in immunology · 2026Review
- Diabetic cardiomyopathy as a disorder of proteostatic maladaptation: context-dependent ubiquitin-specific protease networks.Frontiers in cell and developmental biology · 2026Review
- Inhibition of STING-mediated antiviral innate immunity activation by CD97 via modulation of ER-phagy.Communications biology · 2025Article
- VAPB is a negative regulator of STING-mediated innate immune signaling.Science advances · 2025Article
- Ribosome dysregulation and intervention in age-related infertility.Cell reports. Medicine · 2025Article
- Targeting FAM134B-DDX3X axis inhibiting AKT signaling in hepatocellular carcinoma.Cell death & disease · 2025Article
- USP20 competitively binds to STUB1 to enhance CTSL expression and promote epithelial-mesenchymal transition in head and neck squamous cell carcinoma.Clinical and translational medicine · 2025Article
- Mitophagy as a pivotal axis in non‑alcoholic fatty liver disease: From pathogenic mechanisms to therapeutic strategies (Review).Molecular medicine reports · 2025Review
- Cardiomyocyte USP20 alleviates septic cardiomyopathy by deubiquitinating and inhibiting NLRP3 activity.Clinical and translational medicine · 2025Article
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Authors and funding
8 authors.
Funding
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Abstract
The endoplasmic reticulum (ER) serves as a hub for various cellular processes, and maintaining ER homeostasis is essential for cell function. Reticulophagy is a selective process that removes impaired ER subdomains through autophagy-mediatedlysosomal degradation. While the involvement of ubiquitination in autophagy regulation is well-established, its role in reticulophagy remains unclear. In this study, we screened deubiquitinating enzymes (DUBs) involved in reticulophagy and identified USP20 (ubiquitin specific peptidase 20) as a key regulator of reticulophagy under starvation conditions. USP20 specifically cleaves K48- and K63-linked ubiquitin chains on the reticulophagy receptor RETREG1/FAM134B (reticulophagy regulator 1), thereby stabilizing the substrate and promoting reticulophagy. Remarkably, despite lacking a transmembrane domain, USP20 is recruited to the ER through its interaction with VAPs (VAMP associated proteins). VAPs facilitate the recruitment of early autophagy proteins, including WIPI2 (WD repeat domain, phosphoinositide interacting 2), to specific ER subdomains, where USP20 and RETREG1 are enriched. The recruitment of WIPI2 and other proteins in this process plays a crucial role in facilitating RETREG1-mediated reticulophagy in response to nutrient deprivation. These findings highlight the critical role of USP20 in maintaining ER homeostasis by deubiquitinating and stabilizing RETREG1 at distinct ER subdomains, where USP20 further recruits VAPs and promotes efficient reticulophagy.
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