{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T06:04:23Z","timestamp":1779516263872,"version":"3.53.1"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U24A20814"],"award-info":[{"award-number":["U24A20814"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pathological cardiac hypertrophy is a key risk factor for heart failure (HF). Illustrating the pathogenesis of cardiac hypertrophy may contribute to the treatment of HF. Studies have emphasized that protein ubiquitination is a critical event in HF. In this study, we investigated the role of an E3 ubiquitin ligase, RNF123, in HF induced by angiotensin II (Ang II) infusion and transverse aortic constriction (TAC) surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Heart failure was induced by Ang II infusion or TAC surgery in wild\u2010type and RNF123 knockout mice. Liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) analysis combined with co\u2010immunoprecipitation (Co\u2010IP) was used to identify PRDX1 as an interacting protein of RNF123.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The expression of RNF123 was significantly increased in cardiomyocytes of mice subjected to Ang II infusion or TAC surgery. RNF123 deficiency mitigated cardiac hypertrophy and dysfunction induced by Ang II infusion or TAC operation in mice. In\u00a0vitro, RNF123 knockdown attenuated Ang II\u2010induced hypertrophy, whereas RNF123 overexpression exacerbated the pathological alterations in neonatal rat ventricular myocytes (NRVMs). Mechanistically, LC\u2013MS\/MS and Co\u2010IP assays revealed that RNF123 directly bound to the N\u2010terminal domain of PRDX1 and added a K48\u2010linked ubiquitin chain at the K7 site of PRDX1, subsequently facilitating PRDX1's proteasomal degradation. RNF123\u2010mediated degradation of PRDX1 increased the ROS level in cardiomyocytes, driving the pathogenesis of myocardial hypertrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings identified that cardiomyocyte RNF123 mediates pathological cardiac hypertrophy via ubiquitinating PRDX1 and highlighted that targeting RNF123 may represent a promising therapeutic strategy for HF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70244","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T12:44:51Z","timestamp":1778417091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>E3<\/scp>\n                    Ubiquitin Ligase\n                    <scp>RNF123<\/scp>\n                    Mediates Pathological Cardiac Hypertrophy by Ubiquitinating\n                    <scp>PRDX1<\/scp>\n                    and Upregulating Oxidative Stress in Cardiomyocytes"],"prefix":"10.1111","volume":"242","author":[{"given":"Qinyan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology and Medical Research Center The First Affiliated Hospital, Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Guo","sequence":"additional","affiliation":[{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Medical Research Center The First Affiliated Hospital, Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfu","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Medical Research Center The First Affiliated Hospital, Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy Beihua University  Jilin Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3827-1159","authenticated-orcid":false,"given":"Wu","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Medical Research Center The First Affiliated Hospital, Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1603-3223","authenticated-orcid":false,"given":"Guang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Medical Research Center The First Affiliated Hospital, Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"School of Pharmaceutical Sciences Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010018\u20100007\u2010y"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.065827"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.06.006"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12131780"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2019.12.011"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.106035"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010023\u201000887\u2010x"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.183954"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.10.021"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.12.006"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2024.06.011"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1204"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010021\u201000365\u2010x"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2017.02.012"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556\u2010021\u201000043\u20102"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1194"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14477"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201022\u20103739"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00095\u201023"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201541703"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S195412"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110357"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010023\u201002699\u2010w"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(96)80017-X"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010016\u20102255\u20105"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000254415.31362.a7"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.01.016"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac039"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010020\u20100523\u20102"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421\u2010023\u201000622\u20103"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1320"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.255216"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00026.2013"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tplants.2016.08.002"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311401"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/152308603770380034"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0735\u20101097(00)01123\u20102"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.98.8.794"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8020029"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010021\u201000885\u20105"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2005.7.768"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.02.009"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2405135"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156054"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.23098"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.09.020"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2024.117113"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201055939\u20102"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.11.009"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103392"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.414524"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318866"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9494052"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803749105"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010023\u201005732\u20100"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00923\u201021"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.70244","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apha.70244","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.70244","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:05:15Z","timestamp":1779512715000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.70244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,10]]},"references-count":56,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/apha.70244"],"URL":"https:\/\/doi.org\/10.1111\/apha.70244","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,10]]},"assertion":[{"value":"2025-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70244"}}