{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:21:00Z","timestamp":1778624460756,"version":"3.51.4"},"reference-count":21,"publisher":"The Royal Society","issue":"1879","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"name":"Jiangxi Province Technology Innovation Guidance Program","award":["20203AEI005"],"award-info":[{"award-number":["20203AEI005"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31971041"],"award-info":[{"award-number":["31971041"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82030018"],"award-info":[{"award-number":["82030018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Phil. Trans. R. Soc. B"],"published-print":{"date-parts":[[2023,6,19]]},"abstract":"<jats:p>\n                    The protein expression and function changes from the slow-delayed rectifying\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    current,\n                    <jats:italic>\n                      I\n                      <jats:sub>Ks<\/jats:sub>\n                    <\/jats:italic>\n                    , are tightly associated with ventricular cardiac arrhythmias. Human leukocyte antigen F-associated transcript 10 (FAT10), a member of the ubiquitin-like-modifier family, exerts a protective effect against myocardial ischaemia. However, whether or how FAT10 influences the function of\n                    <jats:italic>\n                      I\n                      <jats:sub>Ks<\/jats:sub>\n                    <\/jats:italic>\n                    remains unclear. Here, human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and\n                    <jats:italic>Fat10<\/jats:italic>\n                    knockout HEK293 (\n                    <jats:italic>\n                      Fat10\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) cells through CRISPR-Cas9 technology were used to evaluate the novel modulation of FAT10 in\n                    <jats:italic>\n                      I\n                      <jats:sub>Ks<\/jats:sub>\n                    <\/jats:italic>\n                    function. Patch-clamp studies showed that the overexpression of FAT10 significantly enhanced the current density of\n                    <jats:italic>\n                      I\n                      <jats:sub>Ks<\/jats:sub>\n                    <\/jats:italic>\n                    both in hiPSC-CMs and HEK293-\n                    <jats:italic>\n                      Fat10\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    cells. In addition, a shortened action potential duration (APD) was seen from hiPSC-CMs transfected with the\n                    <jats:italic>ad-Fat10<\/jats:italic>\n                    virus. Then, a series of molecular approaches from neonatal rat cardiomyocytes, H9C2 cells and HEK293 cells were used to determine the regulatory mechanism of FAT10 in\n                    <jats:italic>\n                      I\n                      <jats:sub>Ks<\/jats:sub>\n                    <\/jats:italic>\n                    . First, western blot assays indicated that the expression of Kv7.1, the alpha-subunit of\n                    <jats:italic>\n                      I\n                      <jats:sub>Ks<\/jats:sub>\n                    <\/jats:italic>\n                    , was increased when FAT10 was overexpressed. Furthermore, immunofluorescence and co-immunoprecipitation assays demonstrated that FAT10 could interact with Kv7.1. Notably, FAT10 impedes Kv7.1 ubiquitination and degradation, thereby stabilizing its expression. Finally, a hypoxia model of hiPSC-CMs was established, and the overexpression of FAT10 showed a protective effect against hypoxia-induced decreases in the current density of\n                    <jats:italic>\n                      I\n                      <jats:sub>Ks<\/jats:sub>\n                    <\/jats:italic>\n                    . Taken together, these findings revealed a novel role of FAT10 in the regulation of the\n                    <jats:italic>\n                      I\n                      <jats:sub>Ks<\/jats:sub>\n                    <\/jats:italic>\n                    potassium channel by competing for Kv7.1 ubiquitination, which provides a new electrophysiological insight that FAT10 could modulate Kv7.1.\n                  <\/jats:p>\n                  <jats:p>This article is part of the theme issue \u2018The heartbeat: its molecular basis and physiological mechanisms\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2022.0167","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T02:39:17Z","timestamp":1682908757000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Human leukocyte antigen F-associated transcript 10 regulates the\n                    <i>\n                      I\n                      <sub>Ks<\/sub>\n                    <\/i>\n                    potassium channel by competing for Kv7.1 ubiquitination"],"prefix":"10.1098","volume":"378","author":[{"given":"Chen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi 330006, People's Republic of China"},{"name":"Jiangxi Key Laboratory of Molecular Medicine, Nanchang of Jiangxi 330006, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi 330006, People's Republic of China"},{"name":"Jiangxi Key Laboratory of Molecular Medicine, Nanchang of Jiangxi 330006, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyan","family":"Xie","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Molecular Medicine, Nanchang of Jiangxi 330006, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi 330006, People's Republic of China"},{"name":"Jiangxi Key Laboratory of Molecular Medicine, Nanchang of Jiangxi 330006, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Wan","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Molecular Medicine, Nanchang of Jiangxi 330006, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9416-0862","authenticated-orcid":true,"given":"Kui","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi 330006, People's Republic of China"},{"name":"Department of Genetic Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi 330006, People's Republic of China"},{"name":"Jiangxi Key Laboratory of Molecular Medicine, Nanchang of Jiangxi 330006, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2023,5]]},"reference":[{"key":"e_1_3_6_2_2","first-page":"99","article-title":"Mutations of voltage-gated ionic channels and risk of severe cardiac arrhythmias","volume":"35","author":"Dehghani-Samani A","year":"2019","unstructured":"Dehghani-Samani A, Madreseh-Ghahfarokhi S, Dehghani-Samani A. 2019 Mutations of voltage-gated ionic channels and risk of severe cardiac arrhythmias. Acta Cardiol. Sin. 35, 99-110. (doi:10.6515\/ACS.201903_35(2).20181028A)","journal-title":"Acta Cardiol. Sin."},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2013.12.004"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1706267114"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.3.917"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00159-0"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00180.2005"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-0933-5"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1747-1028-1-20"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307730"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00144"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12976"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-3118"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.02.008"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03290-3"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.114.001526"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.2.193"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034541"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.09.033"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(98)01491-3"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.09.007"},{"key":"e_1_3_6_22_2","unstructured":"Chen C Zhu X Xie J Li X Wan R Hong K. 2023 Human leukocyte antigen F-associated transcript 10 regulates the I Ks potassium channel by competing for Kv7.1 ubiquitination. Figshare. 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