{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:17:19Z","timestamp":1790252239049,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19H03376"],"award-info":[{"award-number":["JP19H03376"]}],"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":["JP20K06494"],"award-info":[{"award-number":["JP20K06494"]}],"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":["JP20K07058"],"award-info":[{"award-number":["JP20K07058"]}],"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":["JP24K09826"],"award-info":[{"award-number":["JP24K09826"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Calcineurin (CN) is a conserved Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent phosphoprotein phosphatase that plays a key role in Ca<jats:sup>2+<\/jats:sup> signaling. Regulator of calcineurin 1 (RCAN1), also known as Down syndrome critical region gene 1 (DSCR1), interacts with calcineurin and inhibits calcineurin\u2010dependent signaling in various organisms. Ppb1, the fission yeast calcineurin regulates Cl<jats:sup>\u2212<\/jats:sup>\u2010homeostasis, and Ppb1 deletion induces MgCl<jats:sub>2<\/jats:sub> hypersensitivity. Here, we characterize the conserved and novel roles of the fission yeast RCAN1 homolog <jats:italic>rcn1<\/jats:italic><jats:sup>+<\/jats:sup>. Consistent with its role as an endogenous calcineurin inhibitor, Rcn1 overproduction reproduced the calcineurin\u2010null phenotypes, including MgCl<jats:sub>2<\/jats:sub> hypersensitivity and inhibition of calcineurin signaling upon extracellular Ca<jats:sup>2+<\/jats:sup> stimuli as evaluated by the nuclear translocation and transcriptional activation of the calcineurin substrate Prz1. Notably, overexpression of <jats:italic>rcn1<\/jats:italic><jats:sup>+<\/jats:sup> causes hypersensitivity to arsenite, whereas calcineurin deletion induces arsenite tolerance, showing a phenotypic discrepancy between Rcn1 overexpression and calcineurin deletion. Importantly, although Rcn1 deletion induces modest sensitivities to arsenite and MgCl<jats:sub>2<\/jats:sub> in wild\u2010type cells, the arsenite tolerance, but not MgCl<jats:sub>2<\/jats:sub> sensitivity, associated with Ppb1 deletion was markedly suppressed by Rcn1 deletion. Collectively, our findings reveal a previously unrecognized functional collaboration between Rcn1 and calcineurin, wherein Rcn1 not only negatively regulates calcineurin in the Cl<jats:sup>\u2212<\/jats:sup> homeostasis, but also Rcn1 mediates calcineurin signaling to modulate arsenite cytotoxicity.<\/jats:p>","DOI":"10.1111\/gtc.13122","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T04:18:45Z","timestamp":1715141925000},"page":"589-598","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rcn1, the fission yeast homolog of human <scp>DSCR1<\/scp>, regulates arsenite tolerance independently from calcineurin"],"prefix":"10.1111","volume":"29","author":[{"given":"Teruaki","family":"Takasaki","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Bamba","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Kukita","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiko","family":"Nishida","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Kanbayashi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Hagihara","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Osaka Japan"},{"name":"Laboratory of Hygienic Science, Department of Pharmacy, School of Pharmacy Hyogo Medical University  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Satoh","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Laboratory of Pathological Biochemistry Kyoto Pharmaceutical University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6946-0935","authenticated-orcid":false,"given":"Reiko","family":"Sugiura","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2011.00762.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.027201.112"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152665399"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.06.002"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11051034"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1564"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2005.05.002"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/978-1-4614-1533-6_439","volume-title":"Encyclopedia of metalloproteins","author":"Flora S. 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