JP2 and JCN Crosstalk Abrogate MURF1-Mediated JCN Ubiquitination and Degradation in Cardiomyocytes
- JACC Basic Transl Sci. 2026 May;11(5):101534. doi: 10.1016/j.jacbts.2026.101534.
- 1. Northern Jiangsu Cardiovascular Disease Prevention and Treatment Research Institute, Jiangsu University, Zhenjiang, China; Department of Cardiovascular Medicine, Yancheng Third People's Hospital, Yancheng, China; International Genome Center, Jiangsu University, Zhenjiang, China; London Health Sciences Centre Research Institute, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
- 2. School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China.
- 3. Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
- 4. Northern Jiangsu Cardiovascular Disease Prevention and Treatment Research Institute, Jiangsu University, Zhenjiang, China; Department of Cardiovascular Medicine, Yancheng Third People's Hospital, Yancheng, China.
- 5. London Health Sciences Centre Research Institute, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
- 6. Centre of Clinical Laboratory, the First Affiliated Hospital of Soochow University, Suzhou, China.
- 7. Department of Pharmacology, Physiology, and Neurobiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
- 8. London Health Sciences Centre Research Institute, London, Ontario, Canada; Department of Physiology and Pharmacology, Western University, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada.
- 9. Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
- 10. Northern Jiangsu Cardiovascular Disease Prevention and Treatment Research Institute, Jiangsu University, Zhenjiang, China; Department of Cardiothoracic Surgery, Yancheng Third People's Hospital, Yancheng, China.
- 11. Northern Jiangsu Cardiovascular Disease Prevention and Treatment Research Institute, Jiangsu University, Zhenjiang, China; Department of Cardiovascular Medicine, Yancheng Third People's Hospital, Yancheng, China; International Genome Center, Jiangsu University, Zhenjiang, China. Electronic address: [email protected].
- 12. Northern Jiangsu Cardiovascular Disease Prevention and Treatment Research Institute, Jiangsu University, Zhenjiang, China; Department of Cardiovascular Medicine, Yancheng Third People's Hospital, Yancheng, China; London Health Sciences Centre Research Institute, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada. Electronic address: [email protected].
Junctophilin-2 (JP2) and junctin (JCN) are key proteins in maintaining calcium homeostasis in cardiomyocytes. Both are reduced in diseased hearts while overexpression of JP2 mitigates heart failure. This study demonstrates that JP2 and JCN are reduced in cardiomyocytes under stress, leading to intracellular calcium dysregulation and subsequent cell death. JP2 binds JCN, thereby blocking muscle ring finger protein-1 (MURF1)-JCN interaction and subsequently preventing MURF1-mediated JCN ubiquitination and degradation in cardiomyocytes. Thus, JP2 overexpression and MURF1 inhibition similarly preserve JCN protein and attenuate myocardial injury and remodeling, and improve myocardial function in preclinical animal models of lipid overload-induced cardiomyopathy and transverse aortic constriction-induced heart failure. Disruption of the JP2-JCN axis represents an important mechanism underlying heart disease and may serve as a potential therapeutic target for cardiac protection.
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Cat. No.Product NameDescriptionTargetResearch Area
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Research Areas: Neurological Disease