ArticleCirculation research2014
Sumo E2 enzyme UBC9 is required for efficient protein quality control in cardiomyocytes.
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 58 citations in OpenAlex.
- Crosstalk between ubiquitination and other post-translational modifications in cardiovascular diseases.iScience · 2026Review
- The role of SUMOylation in regulating proteins that drive neuronal disease progression.Biochemistry and biophysics reports · 2026Review
- ROS-SUMO Crosstalk in Oxidative Stress: Disease Mechanisms and Reproductive Health.Antioxidants (Basel, Switzerland) · 2026Review
- Arsenome, Arsenobolome, and Arsenobiolome.International journal of molecular sciences · 2025Review
- Article
- 2-Butoxytetrahydrofuran, Isolated fromACS chemical neuroscience · 2024Article
- Ubiquitin-conjugating enzyme E2 for regulating autophagy in diabetic cardiomyopathy: A mini-review.Journal of diabetes · 2024Review
- Protein-protein interaction network-based integration of GWAS and functional data for blood pressure regulation analysis.Human genomics · 2024Article
- Shaping cardiac destiny: the role of post-translational modifications on endoplasmic reticulum - mitochondria crosstalk in cardiac remodeling.Frontiers in pharmacology · 2024Review
- Cardioprotective Strategies After Ischemia-Reperfusion Injury.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Paralogue-Specific Roles of SUMO1 and SUMO2/3 in Protein Quality Control and Associated Diseases.Cells · 2023Review
- Hallmarks of cardiovascular ageing.Nature reviews. Cardiology · 2023Review
- The Prognosis-Predictive and Immunoregulatory Role of SUMOylation Related Genes: Potential Novel Targets in Prostate Cancer Treatment.International journal of molecular sciences · 2023Article
- Targeting calcium regulators as therapy for heart failure: focus on the sarcoplasmic reticulum Ca-ATPase pump.Frontiers in cardiovascular medicine · 2023Review
- Function and regulation of ubiquitin-like SUMO system in heart.Frontiers in cell and developmental biology · 2023Review
- Signalling mechanisms and cellular functions of SUMO.Nature reviews. Molecular cell biology · 2022Review
- Ubiquitin and Ubiquitin-like Proteins in Cancer, Neurodegenerative Disorders, and Heart Diseases.International journal of molecular sciences · 2022Review
- The UBC9/SUMO pathway affects E-cadherin cleavage in HPV-positive head and neck cancer.Frontiers in molecular biosciences · 2022Article
- A high-throughput screening identifies ZNF418 as a novel regulator of the ubiquitin-proteasome system and autophagy-lysosomal pathway.Autophagy · 2021Article
- SUMOylation as a Therapeutic Target for Myocardial Infarction.Frontiers in cardiovascular medicine · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleImpairment of proteasomal function is pathogenic in several cardiac proteinopathies and can eventually lead to heart failure. Loss of proteasomal activity often results in the accumulation of large protein aggregates. The ubiquitin proteasome system (UPS) is primarily responsible for cellular protein degradation, and although the role of ubiquitination in this process is well studied, the function of an ancillary post-translational modification, SUMOylation, in protein quality control is not fully understood.
objectiveTo determine the role of ubiquitin-conjugating enzyme 9 (UBC9), a small ubiquitin-like modifier-conjugating enzyme, in cardiomyocyte protein quality control. METHODS AND
resultsGain- and loss-of-function approaches were used to determine the importance of UBC9. Overexpression of UBC9 enhanced UPS function in cardiomyocytes, whereas knockdown of UBC9 by small interfering RNA caused significant accumulations of aggregated protein. UPS function and relative activity was analyzed using a UPS reporter protein consisting of a short degron, CL1, fused to the COOH-terminus of green fluorescent protein (GFPu). Subsequently, the effects of UBC9 on UPS function were tested in a proteotoxic model of desmin-related cardiomyopathy, caused by cardiomyocyte-specific expression of a mutated αB crystallin, CryAB(R120G). CryAB(R120G) expression leads to aggregate formation and decreased proteasomal function. Coinfection of UBC9-adenovirus with CryAB(R120G) virus reduced the proteotoxic sequelae, decreasing overall aggregate concentrations. Conversely, knockdown of UBC9 significantly decreased UPS function in the model and resulted in increased aggregate levels.
conclusionsUBC9 plays a significant role in cardiomyocyte protein quality control, and its activity can be exploited to reduce toxic levels of misfolded or aggregated proteins in cardiomyopathy.
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