{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:13:15Z","timestamp":1790806395883,"version":"4.1.0"},"reference-count":73,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ferroportin (FPN), the body\u2019s sole iron exporter, is essential for maintaining systemic iron homeostasis. In response to either increased iron or inflammation, hepatocyte-secreted hepcidin binds to FPN, inducing its internalization and subsequent degradation. However, the E3 ubiquitin ligase that underlies FPN degradation has not been identified. Here, we report the identification and characterization of a novel mechanism involving the RNF217-mediated degradation of FPN. A combination of 2 different E3 screens revealed that the Rnf217 gene is a target of Tet1, mediating the ubiquitination and subsequent degradation of FPN. Interestingly, loss of Tet1 expression causes an accumulation of FPN and an impaired response to iron overload, manifested by increased iron accumulation in the liver together with decreased iron in the spleen and duodenum. Moreover, we found that the degradation and ubiquitination of FPN could be attenuated by mutating RNF217. Finally, using 2 conditional knockout mouse lines, we found that knocking out Rnf217 in macrophages increases splenic iron export by stabilizing FPN, whereas knocking out Rnf217 in intestinal cells appears to increase iron absorption. These findings suggest that the Tet1-RNF217-FPN axis regulates iron homeostasis, revealing new therapeutic targets for FPN-related diseases.<\/jats:p>","DOI":"10.1182\/blood.2020008986","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T15:03:17Z","timestamp":1619362997000},"page":"689-705","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":135,"title":["RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity by modulating ferroportin degradation"],"prefix":"10.1182","volume":"138","author":[{"given":"Li","family":"Jiang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China;"},{"name":"The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China;"},{"name":"Department of Nutrition, Precision Nutrition Innovation Center, School of Public Health, Zhengzhou University, Zhengzhou, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7881-7158","authenticated-orcid":false,"given":"Jiaming","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7661-3688","authenticated-orcid":false,"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Precision Nutrition Innovation Center, School of Public Health, Zhengzhou University, Zhengzhou, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9857-2407","authenticated-orcid":false,"given":"Yingying","family":"Yu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Ni","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyang","family":"Zhong","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, State Key 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of Molecular Biology, CAS Center for Excellence in Molecular Cell Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8099-6327","authenticated-orcid":false,"given":"Junxia","family":"Min","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8730-0003","authenticated-orcid":false,"given":"Fudi","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China;"},{"name":"The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China;"},{"name":"Department of Nutrition, Precision Nutrition Innovation Center, School of Public Health, Zhengzhou University, Zhengzhou, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,4,25]]},"reference":[{"issue":"1","key":"2021101815143613600_B1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cell.2010.06.028","article-title":"Two to tango: regulation of Mammalian iron metabolism","volume":"142","author":"Hentze","year":"2010","journal-title":"Cell."},{"issue":"3","key":"2021101815143613600_B2","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2016.12.034","article-title":"A red carpet for iron 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