ArticleThe Journal of clinical investigation2021
Desmosomal COP9 regulates proteome degradation in arrhythmogenic right ventricular dysplasia/cardiomyopathy.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- RhoGEF Ect2 supports RhoA activity at cell-cell junctions through desmoplakin.Life science alliance · 2026Article
- Prevalence, Genetics, and Imaging Characteristics of Patients with Mitral Valve Prolapse and Arrhythmogenic Right Ventricular Cardiomyopathy.medRxiv : the preprint server for health sciences · 2026Article
- Connexin-43 Restoration Alleviates Desmosomal Arrhythmogenic Cardiomyopathy.Circulation. Heart failure · 2026Article
- Cardiomyocyte cytosolic nuclear self-DNA contributes to the pathogenesis of desmoplakin cardiomyopathy.JCI insight · 2025Article
- Machine learning analysis of ARVC informed by sodium channel protein-based interactome networks.Frontiers in pharmacology · 2025Article
- Review
- Genetic inactivation of β-catenin is salubrious, whereas its activation is deleterious in desmoplakin cardiomyopathy.Cardiovascular research · 2023Article
- Plakophilin 2 gene therapy prevents and rescues arrhythmogenic right ventricular cardiomyopathy in a mouse model harboring patient genetics.Nature cardiovascular research · 2023Article
- Arrhythmogenic Cardiomyopathy: from Preclinical Models to Genotype-phenotype Correlation and Pathophysiology.Stem cell reviews and reports · 2023Review
- Cardiomyocyte external mechanical unloading activates modifications of α-actinin differently from sarcomere-originated unloading.The FEBS journal · 2023Article
- Cullin 3 and Blood Pressure Regulation: Insights From Familial Hyperkalemic Hypertension.Hypertension (Dallas, Tex. : 1979) · 2023Review
- EGFR inhibition leads to enhanced desmosome assembly and cardiomyocyte cohesion via ROCK activation.JCI insight · 2023Article
- PANoptosis is a prominent feature of desmoplakin cardiomyopathy.The journal of cardiovascular aging · 2023Article
- Therapeutic efficacy of AAV-mediated restoration of PKP2 in arrhythmogenic cardiomyopathy.Nature cardiovascular research · 2023Article
- Structure and regulation of desmosomes in intercalated discs: Lessons from epithelia.Journal of anatomy · 2023Review
- Desmosomes: emerging pathways and non-canonical functions in cardiac arrhythmias and disease.Biophysical reviews · 2021Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
Dysregulated protein degradative pathways are increasingly recognized as mediators of human disease. This mechanism may have particular relevance to desmosomal proteins that play critical structural roles in both tissue architecture and cell-cell communication, as destabilization/breakdown of the desmosomal proteome is a hallmark of genetic-based desmosomal-targeted diseases, such as the cardiac disease arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, no information exists on whether there are resident proteins that regulate desmosomal proteome homeostasis. Here, we uncovered a cardiac constitutive photomorphogenesis 9 (COP9) desmosomal resident protein complex, composed of subunit 6 of the COP9 signalosome (CSN6), that enzymatically restricted neddylation and targeted desmosomal proteome degradation. CSN6 binding, localization, levels, and function were affected in hearts of classic mouse and human models of ARVD/C affected by desmosomal loss and mutations, respectively. Loss of desmosomal proteome degradation control due to junctional reduction/loss of CSN6 and human desmosomal mutations destabilizing junctional CSN6 were also sufficient to trigger ARVD/C in mice. We identified a desmosomal resident regulatory complex that restricted desmosomal proteome degradation and disease.
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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 Socratic graph.