{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T12:43:09Z","timestamp":1754484189583,"version":"3.40.5"},"reference-count":39,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31701021","81570240","81770281"],"award-info":[{"award-number":["31701021","81570240","81770281"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>RNF4, a poly\u2010SUMO\u2010specific E3 ubiquitin ligase, is associated with protein degradation, DNA damage repair and tumour progression. However, the effect of RNF4 in cardiomyocytes remains to be explored. Here, we identified the alteration of RNF4 from ischaemic hearts and oxidative stress\u2010induced apoptotic cardiomyocytes. Upon myocardial infarction (MI) or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\/ATO treatment, RNF4 increased rapidly and then decreased gradually. PML SUMOylation and PML nuclear body (PML\u2010NB) formation first enhanced and then degraded upon oxidative stress. Reactive oxygen species (ROS) inhibitor was able to attenuate the elevation of RNF4 expression and PML SUMOylation. PML overexpression and RNF4 knockdown by small interfering RNA (siRNA) enhanced PML SUMOylation, promoted p53 recruitment and activation and exacerbated H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\/ATO\u2010induced cardiomyocyte apoptosis which could be partially reversed by knockdown of p53. In vivo, knockdown of endogenous RNF4 via in vivo adeno\u2010associated virus infection deteriorated post\u2010MI structure remodelling including more extensive interstitial fibrosis and severely fractured and disordered structure. Furthermore, knockdown of RNF4 worsened ischaemia\u2010induced cardiac dysfunction of MI models. Our results reveal a novel myocardial apoptosis regulation model that is composed of RNF4, PML and p53. The modulation of these proteins may provide a new approach to tackling cardiac ischaemia.<\/jats:p>","DOI":"10.1111\/jcmm.15363","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:20:44Z","timestamp":1595982044000},"page":"9545-9559","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Knockdown of endogenous RNF4 exacerbates ischaemia\u2010induced cardiomyocyte apoptosis in mice"],"prefix":"10.1111","volume":"24","author":[{"given":"Fang","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P. R. 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