ArticleCirculation research2011
Perturbation of cullin deneddylation via conditional Csn8 ablation impairs the ubiquitin-proteasome system and causes cardiomyocyte necrosis and dilated cardiomyopathy in mice.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 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
- A window into intracellular events in myositis through subcellular proteomics.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Neddylation drives myofibrillogenesis in the developing heart.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Review
- The COP9 signalosome reduces neuroinflammation and attenuates ischemic neuronal stress in organotypic brain slice culture model.Cellular and molecular life sciences : CMLS · 2023Article
- Cullin 3 and Blood Pressure Regulation: Insights From Familial Hyperkalemic Hypertension.Hypertension (Dallas, Tex. : 1979) · 2023Review
- 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
- Necroptosis in heart disease: Molecular mechanisms and therapeutic implications.Journal of molecular and cellular cardiology · 2022Review
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- Exosome-like nanoparticles from Mulberry bark prevent DSS-induced colitis via the AhR/COPS8 pathway.EMBO reports · 2022Article
- Ubiquitin Carboxyl-Terminal Hydrolase L1 of Cardiomyocytes Promotes Macroautophagy and Proteostasis and Protects Against Post-myocardial Infarction Cardiac Remodeling and Heart Failure.Frontiers in cardiovascular medicine · 2022Article
- 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
- Editorial: Post-translational Modifications and Compartmentalized Protein Quality Control in Cardiac Muscle and Disease.Frontiers in physiology · 2021Article
- The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.International journal of molecular sciences · 2020Review
9 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
7 authors at 1 institution in 1 country.
Funding
Abstract
rationaleUbiquitin-proteasome system (UPS) dysfunction has been implicated in cardiac pathogenesis. Understanding how cardiac UPS function is regulated will facilitate delineating the pathophysiological significance of UPS dysfunction and developing new therapeutic strategies. The COP9 (constitutive photomorphogenesis mutant 9) signalosome (CSN) may regulate the UPS, but this has not been tested in a critical vertebrate organ. Moreover, the role of CSN in a postmitotic organ and the impact of cardiomyocyte-restricted UPS dysfunction on the heart have not been reported.
objectiveWe sought to determine the role of CSN-mediated deneddylation in UPS function and postnatal cardiac development and function. METHODS AND
resultsCardiomyocyte-restricted Csn8 gene knockout (CR-Csn8KO) in mice was achieved using a Cre-LoxP system. CR-Csn8KO impaired CSN holocomplex formation and cullin deneddylation and resulted in decreases in F-box proteins. Probing with a surrogate misfolded protein revealed severe impairment of UPS function in CR-Csn8KO hearts. Consequently, CR-Csn8KO mice developed cardiac hypertrophy, which rapidly progressed to heart failure and premature death. Massive cardiomyocyte necrosis rather than apoptosis appears to be the primary cause of the heart failure. This is because (1) massive necrotic cell death and increased infiltration of leukocytes were observed before increased apoptosis; (2) increased apoptosis was not detectable until overt heart failure was observed; and (3) cardiac overexpression of Bcl2 failed to ameliorate CR-Csn8KO mouse premature death.
conclusionsCsn8/CSN plays an essential role in cullin deneddylation, UPS-mediated degradation of a subset of proteins, and the survival of cardiomyocytes and, therefore, is indispensable in postnatal development and function of the heart. Cardiomyocyte-restricted UPS malfunction can cause heart failure.
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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.