{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:13:05Z","timestamp":1788333185403,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21bm0804032h0001"],"award-info":[{"award-number":["JP21bm0804032h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22bm0804032h0002"],"award-info":[{"award-number":["JP22bm0804032h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23bm0804032h0003"],"award-info":[{"award-number":["JP23bm0804032h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["17H06397"],"award-info":[{"award-number":["17H06397"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20H03790"],"award-info":[{"award-number":["20H03790"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K02752"],"award-info":[{"award-number":["25K02752"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>\n                    <jats:italic>RNF213<\/jats:italic>\n                    was originally identified as a susceptibility gene for Moyamoya disease (MMD), and its variants are also associated with other vascular occlusive disorders, including pulmonary arterial hypertension and large\u2010artery atherosclerosis.\n                    <jats:italic>RNF213<\/jats:italic>\n                    encodes a large protein with AAA+ ATPase and E3 ubiquitin ligase activities and has been implicated in vasculopathy as well as cellular responses to microbial infection and lipid stress. However, the precise biological functions of RNF213 and the pathogenic mechanisms underlying disease\u2010associated mutations remain poorly understood. Recent studies have suggested lipid\u2010induced stress may play a key role in MMD pathogenesis. Therefore, we performed temporal transcriptomic analyses to identify RNF213\u2010regulated signaling pathways in response to palmitate, the most common saturated fatty acid. Our results demonstrate that RNF213 is required for activation of apoptosis, the unfolded protein response, and NF\u03baB signaling, as well as for the regulation of autophagy and oxidative stress responses following palmitate exposure. These functions were dependent on both the AAA+ ATPase and RZ\u2010finger domains of RNF213 while MMD\u2010associated RNF213 mutations enhanced palmitate\u2010induced signaling responses. Together, these findings suggest that gain\u2010of\u2010function RNF213 mutations, combined with dysregulated lipid metabolism, contribute to the pathogenesis of RNF213\u2010associated vasculopathies.\n                  <\/jats:p>","DOI":"10.1111\/febs.70712","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:17:01Z","timestamp":1788329821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>RNF213<\/scp>\n                    regulates palmitate signaling through\n                    <scp>AAA<\/scp>\n                    + and\n                    <scp>RZ<\/scp>\n                    \u2010finger domains, a process enhanced by gain\u2010of\u2010function moyamoya disease\u2010associated mutations"],"prefix":"10.1111","author":[{"given":"Qianying","family":"Huang","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biosciences, Graduate School of Medicine Kyoto University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-8578","authenticated-orcid":false,"given":"Tohru","family":"Tezuka","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biosciences, Graduate School of Medicine Kyoto University  Japan"},{"name":"Laboratory of Integrative Molecular Medicine, Graduate School of Medicine Kyoto University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Life Science, Faculty of Science and Engineering Kindai University  Osaka Japan"},{"name":"Center for Cancer Immunotherapy and Immunobiology Kyoto University Graduate School of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Institute of Public Health Kyoto Hokenkai Foundation  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Mineharu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine  Kyoto Japan"},{"name":"Department of Artificial Intelligence in Healthcare and Medicine Kyoto University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsunehiro","family":"Mizushima","sequence":"additional","affiliation":[{"name":"Graduate School of Science, University of Hyogo  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8536-8653","authenticated-orcid":false,"given":"Minsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Molecular Medicine, Graduate School of Medicine Kyoto University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohab","family":"Youssefian","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biosciences, Graduate School of Medicine Kyoto University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0022542","article-title":"Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development","volume":"6","author":"Liu W","year":"2011","journal-title":"PLoS One"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s12199-015-0498-7","article-title":"A new horizon of moyamoya disease and associated health risks explored through RNF213","volume":"21","author":"Koizumi A","year":"2016","journal-title":"Environ Health 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