{"created":"2023-08-02T03:58:05.782556+00:00","id":7240,"links":{},"metadata":{"_buckets":{"deposit":"2bde2b0a-3bae-45ec-bebb-da42f30177c2"},"_deposit":{"created_by":10,"id":"7240","owners":[10],"pid":{"revision_id":0,"type":"depid","value":"7240"},"status":"published"},"_oai":{"id":"oai:repository.lib.tottori-u.ac.jp:00007240","sets":["1:9","2:12"]},"author_link":["26851","765","26852","26853","1879","880","1367","4755","4730","26854","3130","4848","2609","685","1457","3385","26855","4288","26856","26857","26858","26859","26860","26861","26862","26863","26864"],"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2016-10-31","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"5","bibliographicPageEnd":"440","bibliographicPageStart":"433","bibliographicVolumeNumber":"32","bibliographic_titles":[{"bibliographic_title":"Journal of Arrhythmia"},{"bibliographic_title":"Journal of Arrhythmia","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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.","subitem_description_type":"Other"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier B.V."}]},"item_10001_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1016/j.joa.2015.10.005","subitem_relation_type_select":"DOI"}}]},"item_10001_relation_16":{"attribute_name":"情報源","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"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"}]}]},"item_10001_relation_17":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://www.sciencedirect.com/science/article/pii/S188042761500143X"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://www.sciencedirect.com/science/article/pii/S188042761500143X","subitem_relation_type_select":"URI"}}]},"item_10001_rights_15":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2015 Japanese Heart Rhythm Society. Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/"}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"18804276","subitem_source_identifier_type":"ISSN"}]},"item_10001_text_33":{"attribute_name":"著者所属（英）","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science"},{"subitem_text_language":"en","subitem_text_value":"Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science"},{"subitem_text_language":"en","subitem_text_value":"Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science"},{"subitem_text_language":"en","subitem_text_value":"Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science"},{"subitem_text_language":"en","subitem_text_value":"Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science"},{"subitem_text_language":"en","subitem_text_value":"Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center"},{"subitem_text_language":"en","subitem_text_value":"Division of Cardiology and Regenerative Medicine, Nippon Medical School"},{"subitem_text_language":"en","subitem_text_value":"Department of Physiology II, Kanazawa Medical University"},{"subitem_text_language":"en","subitem_text_value":"Department of Pediatrics, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Department of Biological Regulation, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Department of Biological Regulation, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science"},{"subitem_text_language":"en","subitem_text_value":"Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science"},{"subitem_text_language":"en","subitem_text_value":"Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University"}]},"item_10001_version_type_20":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"近藤, 健人"},{"creatorName":"コンドウ, タケヒト","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"久留, 一郎"},{"creatorName":"ヒサトメ, イチロウ","creatorNameLang":"ja-Kana"},{"creatorName":"Hisatome, Ichiro","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Mahati, Endang"},{"creatorName":"マハティ, エンダン","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Notsu, Tomomi"},{"creatorName":"ノツ, トモミ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"李, 佩俐"},{"creatorName":"リ, ペイリ","creatorNameLang":"ja-Kana"},{"creatorName":"Li, Peili","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"飯塚, 和彦"},{"creatorName":"イイズカ, カズヒコ","creatorNameLang":"ja-Kana"},{"creatorName":"Iizuka, Kazuhiko","creatorNameLang":"en"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"加藤, 克"},{"creatorName":"カトウ, マサル","creatorNameLang":"ja-Kana"},{"creatorName":"Kato, Masaru","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"小倉, 一能"},{"creatorName":"オグラ, カズヨシ","creatorNameLang":"ja-Kana"},{"creatorName":"Ogura, Kazuyoshi","creatorNameLang":"en"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"三明, 淳一朗"},{"creatorName":"ミアケ, ジュンイチロウ","creatorNameLang":"ja-Kana"},{"creatorName":"Miake, Junichiro","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"倉田, 康孝"},{"creatorName":"クラタ, ヤスタカ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"坂田, 晋史"},{"creatorName":"サカタ, シンジ","creatorNameLang":"ja-Kana"},{"creatorName":"Sakata, Shinji","creatorNameLang":"en"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"仲宗根, 眞恵"},{"creatorName":"ナカソネ, ナオエ","creatorNameLang":"ja-Kana"},{"creatorName":"Nakasone, Naoe","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"二宮, 治明"},{"creatorName":"ニノミヤ, ハルアキ","creatorNameLang":"ja-Kana"},{"creatorName":"Ninomiya, Haruaki","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"檜垣, 克美"},{"creatorName":"ヒガキ, カツミ","creatorNameLang":"ja-Kana"},{"creatorName":"Higaki, Katsumi","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"河田, 康志"},{"creatorName":"カワタ, ヤスシ","creatorNameLang":"ja-Kana"},{"creatorName":"Kawata, Yasushi","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"白吉, 安昭"},{"creatorName":"シラヨシ, ヤスアキ","creatorNameLang":"ja-Kana"},{"creatorName":"Shirayoshi, Yasuaki","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"ヨシダ, アキオ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"山本, 一博"},{"creatorName":"ヨシダ, アキオ","creatorNameLang":"ja-Kana"},{"creatorName":"Yamamoto, Kazuhiro","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Kondo, Takehito","creatorNameLang":"en"},{"creatorName":"コンドウ, タケヒト","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yoshimura, Shouichi","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Mahati, Endang","creatorNameLang":"en"},{"creatorName":"マハティ, エンダン","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Notsu, Tomomi","creatorNameLang":"en"},{"creatorName":"ノツ, トモミ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Aiba, Takeshi","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Shimizu, Wataru","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kurata, Yasutaka","creatorNameLang":"en"},{"creatorName":"クラタ, ヤスタカ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nakai, Akira","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yoshida, Akio","creatorNameLang":"en"},{"creatorName":"ヨシダ, アキオ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2023-03-17"}],"displaytype":"detail","filename":"ja32(5)_433.pdf","filesize":[{"value":"1.3 MB"}],"format":"application/pdf","licensefree":"© 2015 Japanese Heart Rhythm Society. Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"ja32(5)_433.pdf","url":"https://repository.lib.tottori-u.ac.jp/record/7240/files/ja32(5)_433.pdf"},"version_id":"0688c5b9-416d-4eb5-91fe-f1d855e4f877"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Long QT syndrome","subitem_subject_scheme":"Other"},{"subitem_subject":"Human ether-a-go-go-related gene","subitem_subject_scheme":"Other"},{"subitem_subject":"Heat shock factor","subitem_subject_scheme":"Other"},{"subitem_subject":"Long QT syndrome","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Human ether-a-go-go-related gene","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Heat shock factor","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article"}]},"item_title":"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","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"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","subitem_title_language":"en"}]},"item_type_id":"10001","owner":"10","path":["12","9"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-09-15"},"publish_date":"2021-09-15","publish_status":"0","recid":"7240","relation_version_is_last":true,"title":["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"],"weko_creator_id":"10","weko_shared_id":-1},"updated":"2023-09-29T00:41:12.535270+00:00"}