Journal article
JP2 and JCN Crosstalk Abrogate MURF1-Mediated JCN Ubiquitination and Degradation in Cardiomyocytes
JACC. Basic to translational science, Vol.11(5), 101534
04/17/2026
DOI: 10.1016/j.jacbts.2026.101534
PMCID: PMC13098515
PMID: 42000606
Abstract
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.
Details
- Title: Subtitle
- JP2 and JCN Crosstalk Abrogate MURF1-Mediated JCN Ubiquitination and Degradation in Cardiomyocytes
- Creators
- Xiaoyun Ji - Yancheng Third People's HospitalYifan Huang - Soochow UniversityJinxi Wang - University of IowaZhifeng Dong - Yancheng Third People's HospitalRui Ni - Western UniversityZijun Su - Western UniversityDong Zheng - Soochow UniversityGuo-Chang Fan - University of CincinnatiDouglas L Jones - Western UniversityLong-Sheng Song - University of IowaSubrata Chakrabarti - Western UniversityJianxiang Song - Yancheng Third People's HospitalZhaoliang Su - Yancheng Third People's HospitalTianqing Peng - Western University
- Resource Type
- Journal article
- Publication Details
- JACC. Basic to translational science, Vol.11(5), 101534
- DOI
- 10.1016/j.jacbts.2026.101534
- PMID
- 42000606
- PMCID
- PMC13098515
- NLM abbreviation
- JACC Basic Transl Sci
- ISSN
- 2452-302X
- eISSN
- 2452-302X
- Publisher
- Elsevier Inc.
- Grant note
- Heart and Stroke Foundation of Canada: G-17-0018361 Natural Sciences and Engineering Research Council of Canada: RGPIN/04537-2023 National Natural Science Foundation of China: 32370984 Projects of International Cooperation from Jiangsu: BZ2024031 Key Funds from Health Commission of Jiangsu: ZD2021009 International Science and Technology Cooperation Project from Zhenjiang: GJ2024014 National Heart, Lung, and Blood Institute: R01 HL130346, HL157781, HL157741
This study was supported by the Heart and Stroke Foundation of Canada (G-17-0018361) , the Natural Sciences and Engineering Research Council of Canada (RGPIN/04537-2023) , the National Natural Science Foundation of China (32370984) , Projects of International Cooperation from Jiangsu (BZ2024031) , Key Funds from Health Commission of Jiangsu (ZD2021009) , International Science and Technology Cooperation Project from Zhenjiang (GJ2024014) , and the National Heart, Lung, and Blood Institute (R01 HL130346, HL157781, HL157741, to Dr Song) .
- Language
- English
- Date published
- 04/17/2026
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9985155645802771
Metrics
1 Record Views