ArticleThe American journal of pathology2009
COP9-associated CSN5 regulates exosomal protein deubiquitination and sorting.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- Research on exosomes in cancer multidrug resistance and clinical translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- Desmosome and Hemidesmosome Release via Exosomes from Retinal Pigmented Epithelium - A Precursor to Epithelial-Mesenchymal Transition in Early AMD?Current eye research · 2025Review
- Regulatory Mechanisms and Therapeutic Targeting of PD-L1 Trafficking and Stability in Cancer Immunotherapy.Cancers · 2025Review
- Mapping Organism-wide Single Cell mRNA Expression Linked to Extracellular Vesicle Biogenesis, Secretion, and Cargo.Function (Oxford, England) · 2025Article
- The Silencing of theInternational journal of molecular sciences · 2025Article
- Examination of the enrichment of neuronal extracellular vesicles from cell conditioned media and human plasma using an anti-NCAM immunocapture bead approach.BMC methods · 2025Article
- Article
- COP9 signalosome component CSN-5 stabilizes PUF proteins FBF-1 and FBF-2 in Caenorhabditis elegans germline stem and progenitor cells.Genetics · 2024Article
- Programmed Death Ligand 1 Regulatory Crosstalk with Ubiquitination and Deubiquitination: Implications in Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- OsJAB1 Positively Regulates Ascorbate Biosynthesis and Negatively Regulates Salt Tolerance Due to Inhibiting Early-Stage Salt-Induced ROS Accumulation in Rice.Plants (Basel, Switzerland) · 2023Article
- Regulatory mechanisms and therapeutic potential of JAB1 in neurological development and disorders.Molecular medicine (Cambridge, Mass.) · 2023Review
- Emerging role of ubiquitination/deubiquitination modification of PD-1/PD-L1 in cancer immunotherapy.Genes & diseases · 2023Review
- Regulation of post-translational modification of PD-L1 and advances in tumor immunotherapy.Frontiers in immunology · 2023Review
- Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease.Biomolecules · 2022Review
- K-29 linked ubiquitination of Arrdc4 regulates its function in extracellular vesicle biogenesis.Journal of extracellular vesicles · 2022Article
- Deubiquitinating enzymes (DUBs): Regulation, homeostasis, and oxidative stress response.The Journal of biological chemistry · 2021Review
- Emerging Role of Ubiquitination in the Regulation of PD-1/PD-L1 in Cancer Immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Targeting ubiquitin signaling for cancer immunotherapy.Signal transduction and targeted therapy · 2021Review
- Insights Into Exosomal Non-Coding RNAs Sorting Mechanism and Clinical Application.Frontiers in oncology · 2021Review
- Post-translational Modification Regulates Formation and Cargo-Loading of Extracellular Vesicles.Frontiers in immunology · 2020Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Ubiquitinated endosomal proteins that are deposited into the lumens of multivesicular bodies are either sorted for lysosomal-mediated degradation or secreted as exosomes into the extracellular milieu. The mechanisms that underlie the sorting of cellular cargo proteins are currently unknown. In this study, we show that the COP9 signalosome (CSN)-associated protein CSN5 quantitatively regulated proteins that were sorted into exosomes. Western blot analysis of exosomal proteins indicated that small interfering (si)RNA knockdown of CSN5 results in increased levels of both ubiquitinated and non-ubiquitinated exosomal proteins, including heat shock protein 70, in comparison with exosomes isolated from the supernatants of 293 cells transfected with scrambled siRNA. Furthermore, 293 cells transfected with JAB1/MPN/Mov34 metalloenzyme domain-deleted CSN5 produced exosomes with higher levels of ubiquitinated heat shock protein 70, which did not affect non-ubiquitinated heat shock protein 70 levels. The loss of COP9-associated deubiquitin activity of CSN5 also led to the enhancement of HIV Gag that was sorted into exosomes as well as the promotion of HIV-1 release, suggesting that COP9-associated CSN5 regulates the sorting of a number of exosomal proteins in both a CSN5 JAB1/MPN/Mov34 metalloenzyme domain-dependent and -independent manner. We propose that COP9-associated CSN5 regulates exosomal protein sorting in both a deubiquitinating activity-dependent and -independent manner, which is contrary to the current idea of ubiquitin-dependent sorting of proteins to exosomes.
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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.