ArticleCirculation2011
COP9 signalosome regulates autophagosome maturation.
Article in Circulation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- COP9 signalosome deneddylation activity is required for proliferation but not dedifferentiation of vascular smooth muscle cells in neointimal hyperplasia.American journal of physiology. Heart and circulatory physiology · 2026Article
- Epigenetic Aging in Brain Tissue of the Self-Fertilizing Vertebrate,Ecology and evolution · 2026Article
- Extracellular granzyme K enhances PD-L1 transcription and stability via F2RL1 activation to facilitate tumor immune evasion in lung adenocarcinoma.Journal for immunotherapy of cancer · 2026Article
- A window into intracellular events in myositis through subcellular proteomics.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Csn5 inhibits autophagy by regulating the ubiquitination of Atg6 and Tor to mediate the pathogenicity of Magnaporthe oryzae.Cell communication and signaling : CCS · 2024Article
- mTORC1 hyperactivation and resultant suppression of macroautophagy contribute to the induction of cardiomyocyte necroptosis by catecholamine surges.Physiological reports · 2024Article
- Review
- The impact of a polyphenol-rich supplement on epigenetic and cellular markers of immune age: a pilot clinical study.Frontiers in nutrition · 2024Article
- Mitochondria are secreted in extracellular vesicles when lysosomal function is impaired.Nature communications · 2023Article
- The COPS3-FOXO3 positive feedback loop regulates autophagy to promote cisplatin resistance in osteosarcoma.Autophagy · 2023Article
- The Interplay Between Autophagy and Regulated Necrosis.Antioxidants & redox signaling · 2023Review
- Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation.Cell reports · 2023Article
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells.Molecular medicine reports · 2021Article
- TRIM39 deficiency inhibits tumor progression and autophagic flux in colorectal cancer via suppressing the activity of Rab7.Cell death & disease · 2021Article
- FYCO1 Regulates Cardiomyocyte Autophagy and Prevents Heart Failure Due to Pressure Overload In Vivo.JACC. Basic to translational science · 2021Article
- Cell death in head and neck cancer pathogenesis and treatment.Cell death & disease · 2021Review
- Catecholamine Surges Cause Cardiomyocyte NecroptosisFrontiers in cardiovascular medicine · 2021Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAutophagy is essential to intracellular homeostasis and is involved in the pathophysiology of a variety of diseases. Mechanisms regulating selective autophagy remain poorly understood. The COP9 signalosome (CSN) is a conserved protein complex consisting of 8 subunits (CSN1 through CSN8), and is known to regulate the ubiquitin-proteasome system. However, it is unknown whether CSN plays a role in autophagy. METHODS AND
resultsMarked increases in the LC3-II and p62 proteins were observed on Csn8 depletion in the cardiomyocytes of mouse hearts with cardiomyocyte-restricted knockout of the gene encoding CSN subunit 8 (CR-Csn8KO). The increases in autophagosomes were confirmed by probing with green fluorescent protein-LC3 and electron microscopy. Autophagic flux assessments revealed that defective autophagosome removal was the cause of autophagosome accumulation and occurred before a global ubiquitin-proteasome system impairment in Csn8-deficient hearts. Analyzing the prevalence of different stages of autophagic vacuoles revealed defective autophagosome maturation. Downregulation of Rab7 was found to colocalize strikingly with the autophagosome accumulation at the individual cardiomyocyte level. A significantly higher percent of cardiomyocytes with autophagosome accumulation underwent necrosis in CR-Csn8KO hearts. Long-term lysosomal inhibition with chloroquine induced cardiomyocyte necrosis in mice. Rab7 knockdown impaired autophagosome maturation of nonselective and selective autophagy and exacerbated cell death induced by proteasome inhibition in cultured cardiomyocytes.
conclusionsCsn8/CSN is a central regulator in not only the proteasomal proteolytic pathway, but also selective autophagy. Likely through regulating the expression of Rab7, Csn8/CSN plays a critical role in autophagosome maturation. Impaired autophagosome maturation causes cardiomyocytes to undergo necrosis.
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Registered trials
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.