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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
https://repository.lib.tottori-u.ac.jp/records/7240
https://repository.lib.tottori-u.ac.jp/records/72404e33a46b-374a-4285-8590-ea95895940b8
| 名前 / ファイル | ライセンス | アクション |
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ja32(5)_433.pdf (1.3 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||||||||||||||
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| 公開日 | 2021-09-15 | |||||||||||||||||
| タイトル | ||||||||||||||||||
| 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 | |||||||||||||||||
| 言語 | en | |||||||||||||||||
| 言語 | ||||||||||||||||||
| 言語 | eng | |||||||||||||||||
| キーワード | ||||||||||||||||||
| 主題 | Long QT syndrome | |||||||||||||||||
| キーワード | ||||||||||||||||||
| 主題 | Human ether-a-go-go-related gene | |||||||||||||||||
| キーワード | ||||||||||||||||||
| 主題 | Heat shock factor | |||||||||||||||||
| キーワード | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 主題 | Long QT syndrome | |||||||||||||||||
| キーワード | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 主題 | Human ether-a-go-go-related gene | |||||||||||||||||
| キーワード | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 主題 | Heat shock factor | |||||||||||||||||
| 資源タイプ | ||||||||||||||||||
| 資源タイプ | journal article | |||||||||||||||||
| 著者 |
近藤, 健人
× 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
WEKO
4730
× 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
WEKO
3385
× 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） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University | |||||||||||||||||
| 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 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 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 | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Division of Cardiology and Regenerative Medicine, Nippon Medical School | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Department of Physiology II, Kanazawa Medical University | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Department of Pediatrics, Faculty of Medicine, Tottori University | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Department of Biological Regulation, Faculty of Medicine, Tottori University | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Department of Biological Regulation, Faculty of Medicine, Tottori University | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University | |||||||||||||||||
| 著者所属（英） | ||||||||||||||||||
| 言語 | en | |||||||||||||||||
| 値 | Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University | |||||||||||||||||
| 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 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 | ||||||||||||||||||
| 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 | Elsevier B.V. | |||||||||||||||||
| ISSN | ||||||||||||||||||
| 収録物識別子タイプ | ISSN | |||||||||||||||||
| 収録物識別子 | 18804276 | |||||||||||||||||
| DOI | ||||||||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||||||||
| 識別子タイプ | DOI | |||||||||||||||||
| 関連識別子 | 10.1016/j.joa.2015.10.005 | |||||||||||||||||
| 権利 | ||||||||||||||||||
| 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 | ||||||||||||||||||
| 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 | ||||||||||||||||||
| 識別子タイプ | URI | |||||||||||||||||
| 関連識別子 | https://www.sciencedirect.com/science/article/pii/S188042761500143X | |||||||||||||||||
| 関連名称 | https://www.sciencedirect.com/science/article/pii/S188042761500143X | |||||||||||||||||
| 著者版フラグ | ||||||||||||||||||
| 出版タイプ | VoR | |||||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||||||||
