title: Ubiquitin-specific protease 14 regulates cardiac hypertrophy progression by increasing GSK-3β phosphorylation.
abstract: Cardiac hypertrophy, a compensatory response to various stimuli in the heart, independently predicts cardiovascular ailments and related deaths. Increasing evidence indicates ubiquitin-proteasome signaling contributes to cardiac hypertrophy regulation. Here, we identified ubiquitin-specific protease 14 (USP14), a 19S proteasome associated deubiquitinase (DUB), as a novel target for cardiac hypertrophy therapy via inhibition of the GSK-3β pathway. Indeed, USP14 expression was increased in an animal model of abdominal aorta constriction. In an angiotensin II (AngII) induced primary neonatal rat cardiomyocyte hypertrophy model, USP14 expression was increased in a time-dependent manner, and reduced USP14 deubiquitinase activity or USP14 knockdown resulted in lower expression levels of the myocardial hypertrophy specific marker β-MHC, and subsequent decreased GSK-3β phosphorylation. In conclusion, USP14 mediates the development of cardiac hypertrophy by promoting GSK-3β phosphorylation, suggesting that USP14 might represent a novel therapeutic target for cardiac hypertrophy treatment.
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chai
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.
authors.forename: Shuangwei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangdong, 510182, China.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangdong, 510182, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Cai
authors.affiliation: Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangdong, 510182, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xia
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Li
authors.affiliation: Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangdong, 510182, China.
authors.forename: Jinbao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangdong, 510182, China. Electronic address: hhb800616@126.com.
authors.forename: Hongbiao
authors.initials: H
authors.lastname: Huang
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China. Electronic address: gzliushiming@126.com.
authors.forename: Shiming
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology*; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006352:Heart Ventricles / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C000609601:USP14 protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; D043222:Ubiquitin Thiolesterase; D018995:Myosin Heavy Chains
keywords: Cardiac hypertrophy; Deubiquitinase; GSK-3β; USP14