ArticleCirculation. Heart failure2013
The COP9 signalosome is required for autophagy, proteasome-mediated proteolysis, and cardiomyocyte survival in adult mice.
Article in Circulation. Heart failure, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- 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
- A window into intracellular events in myositis through subcellular proteomics.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- mTORC1 hyperactivation and resultant suppression of macroautophagy contribute to the induction of cardiomyocyte necroptosis by catecholamine surges.Physiological reports · 2024Article
- Review
- Cullin 3 and Blood Pressure Regulation: Insights From Familial Hyperkalemic Hypertension.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation.Cell reports · 2023Article
- The COP9 signalosome complex regulates fungal development and virulence in the wheat scab fungusFrontiers in microbiology · 2023Article
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling.EMBO reports · 2021Article
- Cardioprotective effect of MLN4924 on ameliorating autophagic flux impairment in myocardial ischemia-reperfusion injury by Sirt1.Redox biology · 2021Article
- Desmosomal COP9 regulates proteome degradation in arrhythmogenic right ventricular dysplasia/cardiomyopathy.The Journal of clinical investigation · 2021Article
- The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.International journal of molecular sciences · 2020Review
- The necessity of NEDD8/Rub1 for vitality and its association with mitochondria-derived oxidative stress.Redox biology · 2020Review
- COP9 Signalosome Suppresses RIPK1-RIPK3-Mediated Cardiomyocyte Necroptosis in Mice.Circulation. Heart failure · 2020Article
- Priming the Proteasome to Protect against Proteotoxicity.Trends in molecular medicine · 2020Review
- Neddylation, an Emerging Mechanism Regulating Cardiac Development and Function.Frontiers in physiology · 2020Review
- Conceptual Evolution of Cell Signaling.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThe COP9 signalosome (CSN) is an evolutionarily conserved protein complex composed of 8 unique protein subunits (CSN1 through CSN8). We have recently discovered in perinatal mouse hearts that CSN regulates not only proteasome-mediated proteolysis but also macroautophagy. However, the physiological significance of CSN in a post-mitotic organ of adult vertebrates has not been determined. We sought to study the physiological role of CSN8/CSN in adult mouse hearts. METHODS AND
resultsCsn8 was conditionally ablated in the cardiomyocytes of adult mice (CSN8(CKO)) using a temporally controlled Cre-LoxP system. Loss of CSN8 accumulated the neddylated forms of cullins and noncullin proteins, increased ubiquitinated proteins, and stabilized a surrogate substrate of the proteasome in the heart. Autophagic flux was significantly decreased, whereas autophagosomes were markedly increased in CSN8(CKO) hearts, indicative of impaired autophagosome removal. Furthermore, we observed increased oxidized proteins, massive necrotic cardiomyocytes, and morphological and functional changes characteristic of dilated cardiomyopathy in CSN8(CKO) mice.
conclusionsCSN deneddylates substrates more than cullins and is indispensable to cardiomyocyte survival in not only perinatal hearts but also adult hearts. CSN8/CSN regulates both proteasome-mediated proteolysis and the autophagic-lysosomal pathway, critical to the removal of oxidized proteins in the heart.
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Registered trials
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