| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2021-09-15 |
| タイトル |
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タイトル |
Characterization of the novel mutant A78T-HERG from a long QT syndrome type 2 patient: Instability of the mutant protein and stabilization by heat shock factor 1 |
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言語 |
en |
| 言語 |
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言語 |
eng |
| キーワード |
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主題Scheme |
Other |
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主題 |
Long QT syndrome |
| キーワード |
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主題Scheme |
Other |
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主題 |
Human ether-a-go-go-related gene |
| キーワード |
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主題Scheme |
Other |
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主題 |
Heat shock factor |
| キーワード |
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言語 |
en |
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主題Scheme |
Other |
|
主題 |
Long QT syndrome |
| キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Human ether-a-go-go-related gene |
| キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Heat shock factor |
| 資源タイプ |
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資源タイプ |
journal article |
| 著者 |
近藤, 健人
久留, 一郎
Mahati, Endang
Notsu, Tomomi
李, 佩俐
飯塚, 和彦
加藤, 克
小倉, 一能
三明, 淳一朗
倉田, 康孝
坂田, 晋史
仲宗根, 眞恵
二宮, 治明
檜垣, 克美
河田, 康志
白吉, 安昭
ヨシダ, アキオ
山本, 一博
Kondo, Takehito
Yoshimura, Shouichi
Mahati, Endang
Notsu, Tomomi
Aiba, Takeshi
Shimizu, Wataru
Kurata, Yasutaka
Nakai, Akira
Yoshida, Akio
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| 著者所属（英） |
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言語 |
en |
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値 |
Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University |
| 著者所属（英） |
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言語 |
en |
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値 |
Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science |
| 著者所属（英） |
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言語 |
en |
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値 |
Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science |
| 著者所属（英） |
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言語 |
en |
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値 |
Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science |
| 著者所属（英） |
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言語 |
en |
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値 |
Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science |
| 著者所属（英） |
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言語 |
en |
|
値 |
Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science |
| 著者所属（英） |
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言語 |
en |
|
値 |
Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University |
| 著者所属（英） |
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言語 |
en |
|
値 |
Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University |
| 著者所属（英） |
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言語 |
en |
|
値 |
Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University |
| 著者所属（英） |
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言語 |
en |
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値 |
Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University |
| 著者所属（英） |
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言語 |
en |
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値 |
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center |
| 著者所属（英） |
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言語 |
en |
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値 |
Division of Cardiology and Regenerative Medicine, Nippon Medical School |
| 著者所属（英） |
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言語 |
en |
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値 |
Department of Physiology II, Kanazawa Medical University |
| 著者所属（英） |
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言語 |
en |
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値 |
Department of Pediatrics, Faculty of Medicine, Tottori University |
| 著者所属（英） |
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言語 |
en |
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値 |
Department of Biological Regulation, Faculty of Medicine, Tottori University |
| 著者所属（英） |
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言語 |
en |
|
値 |
Department of Biological Regulation, Faculty of Medicine, Tottori University |
| 著者所属（英） |
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言語 |
en |
|
値 |
Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine |
| 著者所属（英） |
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言語 |
en |
|
値 |
Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University |
| 著者所属（英） |
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言語 |
en |
|
値 |
Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University |
| 著者所属（英） |
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言語 |
en |
|
値 |
Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science |
| 著者所属（英） |
|
|
言語 |
en |
|
値 |
Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science |
| 著者所属（英） |
|
|
言語 |
en |
|
値 |
Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University |
| 抄録 |
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内容記述タイプ |
Other |
|
内容記述 |
Background:The human ether-a-go-go-related gene (HERG) encodes the α-subunit of rapidly activating delayed-rectifier potassium channels. Mutations in this gene cause long QT syndrome type 2 (LQT2). In most cases, mutations reduce the stability of the channel protein, which can be restored by heat shock (HS). Methods: We identified the novel mutant A78T-HERG in a patient with LQT2. The purpose of the current study was to characterize this mutant protein and test whether HS and heat shock factors (HSFs) could stabilize the mutant protein. A78T-HERG and wild-type HERG (WT-HERG) were expressed in HEK293 cells and analyzed by immunoblotting, immunoprecipitation, immunofluorescence, and whole-cell patch clamping. Results: When expressed in HEK293 cells, WT-HERG gave rise to immature and mature forms of the protein at 135 and 155 kDa, respectively. A78T-HERG gave rise only to the immature form, which was heavily ubiquitinated. The proteasome inhibitor MG132 increased the expression of immature A78T-HERG and increased both the immature and mature forms of WT-HERG. WT-HERG, but not A78T-HERG, was expressed on the plasma membrane. In whole-cell patch clamping experiments, depolarizing pulses evoked E4031-sensitive HERG channel currents in cells transfected with WT-HERG, but not in cells transfected with A78T-HERG. The A78V mutant, but not A78G mutant, remained in the immature form similarly to A78T. Maturation of the A78T-HERG protein was facilitated by HS, expression of HSF-1, or exposure to geranyl geranyl acetone. Conclusions: A78T-HERG was characterized by protein instability and reduced expression on the plasma membrane. The stability of the mutant was partially restored by HSF-1, indicating that HSF-1 is a target for the treatment for LQT2 caused by the A78T mutation in HERG. |
| 書誌情報 |
Journal of Arrhythmia
en : Journal of Arrhythmia
巻 32,
号 5,
p. 433-440,
発行日 2016-10-31
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| 出版者 |
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出版者 |
Elsevier B.V. |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
18804276 |
| DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
10.1016/j.joa.2015.10.005 |
| 権利 |
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権利情報 |
© 2015 Japanese Heart Rhythm Society. Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| 情報源 |
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関連名称 |
Kondo, Takehito. Hisatome, Ichiro. Yoshimura, Shouichi. et al. Characterization of the novel mutant A78T-HERG from a long QT syndrome type 2 patient: Instability of the mutant protein and stabilization by heat shock factor 1. Journal of Arrhythmia. 32. 43 |
| 関連サイト |
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識別子タイプ |
URI |
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関連識別子 |
https://www.sciencedirect.com/science/article/pii/S188042761500143X |
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関連名称 |
https://www.sciencedirect.com/science/article/pii/S188042761500143X |
| 著者版フラグ |
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出版タイプ |
VoR |
ja32(5)_433.pdf (1.3 MB)
