UBC9 regulates cardiac sodium channel Nav1.5 ubiquitination, degradation and sodium current density.
Bo Tang,Y. T. Hu,Zhijie Wang,Chen Cheng,Pengyun Wang,Lina Liang,Hongbo Xiong,Chunyan Luo,Chengqi Xu,Qiuyun Chen,Qiuyun Chen,Qing Kenneth Wang +11 more
TLDR
It is shown that UBC9, a SUMO-conjugating enzyme, regulates ubiquitination and degradation of Nav1.5, and co-immunoprecipitation showed that U BC9 interacts with Nedd4-2, which acts as an E3 ubiquitin-protein ligase involved in ubiquitine-protein degradation and regulates Nav 1.5 expression levels in asumOylation-independent manner.Citations
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Inhibition of the Ubc9 E2 SUMO-conjugating enzyme-CRMP2 interaction decreases NaV1.7 currents and reverses experimental neuropathic pain
Liberty François-Moutal,Erik T. Dustrude,Yue Wang,Tatiana Brustovetsky,Angie Dorame,Weina Ju,Aubin Moutal,Samantha Perez-Miller,Nickolay Brustovetsky,Vijay Gokhale,May Khanna,Rajesh Khanna +11 more
TL;DR: Structural modeling has now identified a pocket-harboring CRMP2's SUMOylation motif that, when targeted through computational screening of ligands/molecules, is expected to identify small molecules that will biochemically and functionally target CRMP1.7 currents and reverse neuropathic pain.
Journal ArticleDOI
Endothelial Cell Metabolic Memory Causes Cardiovascular Dysfunction In Diabetes.
Yufeng Yao,Qixue Song,Changqing Hu,Xingwen Da,Yubing Yu,Zuhan He,Chengqi Xu,Qiuyun Chen,Qiuyun Chen,Qing Kenneth Wang +9 more
TL;DR: In this paper, the authors identify the molecular mechanism for hyperglycemia-induced metabolic memory in endothelial cells (ECs), and show its critical importance to development of cardiovascular dysfunction in diabetes.
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Life Cycle of the Cardiac Voltage-Gated Sodium Channel NaV1.5.
TL;DR: In this paper, a variety of protein partners are needed to achieve the balance between SCN5A transcription and mRNA decay, endoplasmic reticulum retention and export, Golgi apparatus retention, selective anchoring and degradation, activation, and inactivation of sodium currents.
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FAT10 protects against ischemia-induced ventricular arrhythmia by decreasing Nedd4-2/Nav1.5 complex formation.
Xiao Liu,Jin Ge,Chen Chen,Yang Shen,Jinyan Xie,Xin Zhu,Menglu Liu,Jinzhu Hu,Leifeng Chen,Linjuan Guo,Qiongqiong Zhou,Xia Yan,Yuming Qiu,Rong Wan,Ali J. Marian,Kui Hong +15 more
TL;DR: In this article, the role of the human leukocyte antigen F-associated transcript 10 (FAT10) is investigated in regulating the sodium channel Nav1.5, a major regulator of cardiac arrhythmias.
Journal ArticleDOI
The endosomal trafficking regulator LITAF controls the cardiac Nav1.5 channel via the ubiquitin ligase NEDD4-2.
Nilüfer N. Turan,Karni S. Moshal,Karim Roder,Brett Baggett,Anatoli Y. Kabakov,Saroj Dhakal,Ryota Teramoto,David Y. Chiang,Mingwang Zhong,An Xie,Yichun Lu,Samuel C. Dudley,Calum A. MacRae,Alain Karma,Gideon Koren +14 more
TL;DR: Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening, and corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation.
References
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Journal ArticleDOI
The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
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Genetic basis and molecular mechanism for idiopathic ventricular fibrillation
Qiuyun Chen,Glenn E. Kirsch,Danmei Zhang,Ramon Brugada,Josep Brugada,Pedro Brugada,Domenico Potenza,Angel Moya,Martin Borggrefe,Günter Breithardt,Rocio Ortiz-Lopez,Zhiqing Wang,Charles Antzelevitch,Richard E. O'Brien,Eric Schulze-Bahr,Mark T. Keating,Jeffrey A. Towbin,Qing Wang +17 more
TL;DR: It is shown that sodium channels with the missense mutation recover from inactivation more rapidly than normal and that the frameshift mutation causes the sodium channel to be non-functional.
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SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome
Qing Kenneth Wang,Jiaxiang Shen,Jiaxiang Shen,Igor Splawski,Donald L. Atkinson,Donald L. Atkinson,Zhizhong Li,Jennifer L. Robinson,Arthur J. Moss,Jeffrey A. Towbin,Mark T. Keating +10 more
TL;DR: Genetic linkage between LQT3 and polymorphisms within SCN5A, the cardiac sodium channel gene, and single strand conformation polymorphism and DNA sequence analyses suggest that mutations in SCN 5A cause chromosome 3-linked LQt and indicate a likely cellular mechanism for this disorder.
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Sumoylation: A Regulatory Protein Modification in Health and Disease
Annette Flotho,Frauke Melchior +1 more
TL;DR: Basic mechanisms and recent developments in the physiology of sumoylation are highlighted and it is not surprising that disease links are beginning to emerge and that interference withsumoylation is being considered for intervention.
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An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.
Jamie D. Kapplinger,David J. Tester,Marielle Alders,Begoña Benito,Myriam Berthet,Josep Brugada,Pedro Brugada,Véronique Fressart,Alejandra Guerchicoff,Carole Harris-Kerr,Shiro Kamakura,Florence Kyndt,Florence Kyndt,Tamara T. Koopmann,Yoshihiro Miyamoto,Ryan Pfeiffer,Guido D. Pollevick,Vincent Probst,Sven Zumhagen,Matteo Vatta,Jeffrey A. Towbin,Wataru Shimizu,Eric Schulze-Bahr,Charles Antzelevitch,Benjamin A. Salisbury,Pascale Guicheney,Arthur A.M. Wilde,Ramon Brugada,Jean-Jacques Schott,Jean-Jacques Schott,Jean-Jacques Schott,Michael J. Ackerman +31 more
TL;DR: Overall, 21% of BrS probands have mutations in SCN5A compared to the 2% to 5% background rate of rare variants reported in healthy control subjects, which may help further distinguish pathogenic mutations from similarly rare but otherwise innocuous ones found in cases.