ArticleThe Journal of biological chemistry2015
Phosphorylation of the deubiquitinase USP20 by protein kinase A regulates post-endocytic trafficking of β2 adrenergic receptors to autophagosomes during physiological stress.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Targeting β2-Adrenergic Receptor Stability With Lycorine Reveals a Host-Directed Pathway for Antiviral Defense Against Poxviruses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of ubiquitin system in ageing-related diseases and potential therapeutic opportunities.Molecular biomedicine · 2026Review
- USP20 as a key regulator of immunosuppression and a novel predictor of poor prognosis in lung adenocarcinoma.Biology direct · 2026Article
- USP20 deletion promotes eccentric cardiac remodeling in response to pressure overload and increases mortality.American journal of physiology. Heart and circulatory physiology · 2024Article
- Adrenoceptor Desensitization: Current Understanding of Mechanisms.Pharmacological reviews · 2024Review
- The emerging role of ubiquitin-specific protease 20 in tumorigenesis and cancer therapeutics.Cell death & disease · 2022Review
- A single phenylalanine residue in β-arrestin2 critically regulates its binding to G protein-coupled receptors.The Journal of biological chemistry · 2022Article
- Decreased MEF2A Expression Regulated by Its Enhancer Methylation Inhibits Autophagy and May Play an Important Role in the Progression of Alzheimer's Disease.Frontiers in neuroscience · 2021Article
- Structural and functional studies of USP20 ZnF-UBP domain by NMR.Protein science : a publication of the Protein Society · 2019Article
- The deubiquitinase ubiquitin-specific protease 20 is a positive modulator of myocardial βThe Journal of biological chemistry · 2019Article
- Endo-lysosomal sorting of G-protein-coupled receptors by ubiquitin: Diverse pathways for G-protein-coupled receptor destruction and beyond.Traffic (Copenhagen, Denmark) · 2019Review
- USP20 (Ubiquitin-Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Review
- The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy initiation.EMBO reports · 2018Article
- Multiple Transceptors for Macro- and Micro-Nutrients Control Diverse Cellular Properties Through the PKA Pathway in Yeast: A Paradigm for the Rapidly Expanding World of Eukaryotic Nutrient Transceptors Up to Those in Human Cells.Frontiers in pharmacology · 2018Review
- GPCR desensitization: Acute and prolonged phases.Cellular signalling · 2018Review
- Mdm2 regulates cardiac contractility by inhibiting GRK2-mediated desensitization of β-adrenergic receptor signaling.JCI insight · 2017Article
- Regulation of G Protein-Coupled Receptors by Ubiquitination.International journal of molecular sciences · 2017Review
- Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of β-Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor κB (NFκB) Activation.The Journal of biological chemistry · 2016Article
- Recycling and Endosomal Sorting of Protease-activated Receptor-1 Is Distinctly Regulated by Rab11A and Rab11B Proteins.The Journal of biological chemistry · 2016Article
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3 authors.
Funding
Abstract
Ubiquitination by the E3 ligase Nedd4 and deubiquitination by the deubiquitinases USP20 and USP33 have been shown to regulate the lysosomal trafficking and recycling of agonist-activated β2 adrenergic receptors (β2ARs). In this work, we demonstrate that, in cells subjected to physiological stress by nutrient starvation, agonist-activated ubiquitinated β2ARs traffic to autophagosomes to colocalize with the autophagy marker protein LC3-II. Furthermore, this trafficking is synchronized by dynamic posttranslational modifications of USP20 that, in turn, are induced in a β2AR-dependent manner. Upon β2AR activation, a specific isoform of the second messenger cAMP-dependent protein kinase A (PKAα) rapidly phosphorylates USP20 on serine 333 located in its unique insertion domain. This phosphorylation of USP20 correlates with a characteristic SDS-PAGE mobility shift of the protein, blocks its deubiquitinase activity, promotes its dissociation from the activated β2AR complex, and facilitates trafficking of the ubiquitinated β2AR to autophagosomes, which fuse with lysosomes to form autolysosomes where receptors are degraded. Dephosphorylation of USP20 has reciprocal effects and blocks trafficking of the β2AR to autophagosomes while promoting plasma membrane recycling of internalized β2ARs. Our findings reveal a dynamic regulation of USP20 by site-specific phosphorylation as well as the interdependence of signal transduction and trafficking pathways in balancing adrenergic stimulation and maintaining cellular homeostasis.
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