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In contrast, the renal lesion in\n                    <jats:styled-content>c<\/jats:styled-content>\n                    ongenital\n                    <jats:styled-content>p<\/jats:styled-content>\n                    olycystic\n                    <jats:styled-content>k<\/jats:styled-content>\n                    idney (\n                    <jats:italic>cpk<\/jats:italic>\n                    ) mice, with a mutation in\n                    <jats:italic>Cys1 and<\/jats:italic>\n                    cystin protein loss, closely phenocopies ARPKD. Although the nonhomologous mutation diminished the translational relevance of the\n                    <jats:italic>cpk<\/jats:italic>\n                    model, recent identification of patients with\n                    <jats:italic>CYS1<\/jats:italic>\n                    mutations and ARPKD prompted the investigations described herein. We examined cystin and FPC expression in mouse models (\n                    <jats:italic>cpk<\/jats:italic>\n                    , rescued\u2010\n                    <jats:italic>cpk<\/jats:italic>\n                    (r\u2010\n                    <jats:italic>cpk<\/jats:italic>\n                    ),\n                    <jats:italic>Pkhd1<\/jats:italic>\n                    mutants) and mouse cortical collecting duct (CCD) cell lines (wild type (\n                    <jats:italic>wt<\/jats:italic>\n                    ),\n                    <jats:italic>cpk<\/jats:italic>\n                    ). We found that cystin deficiency caused FPC loss in both\n                    <jats:italic>cpk<\/jats:italic>\n                    kidneys and CCD cells. FPC levels increased in r\n                    <jats:italic>\u2010cpk<\/jats:italic>\n                    kidneys and siRNA of\n                    <jats:italic>Cys1<\/jats:italic>\n                    in\n                    <jats:italic>wt<\/jats:italic>\n                    cells reduced FPC. However, FPC deficiency in\n                    <jats:italic>Pkhd1<\/jats:italic>\n                    mutants did not affect cystin levels. Cystin deficiency and associated FPC loss impacted the architecture of the primary cilium, but not ciliogenesis. No reduction in\n                    <jats:italic>Pkhd1<\/jats:italic>\n                    mRNA levels in\n                    <jats:italic>cpk<\/jats:italic>\n                    kidneys and CCD cells suggested posttranslational FPC loss. Studies of cellular protein degradation systems suggested selective autophagy as a mechanism. In support of the previously described function of FPC in E3 ubiquitin ligase complexes, we demonstrated reduced polyubiquitination and elevated levels of functional epithelial sodium channel in\n                    <jats:italic>cpk<\/jats:italic>\n                    cells. Therefore, our studies expand the function of cystin in mice to include inhibition of\n                    <jats:italic>Myc<\/jats:italic>\n                    expression via interaction with necdin and maintenance of FPC as functional component of the NEDD4 E3 ligase complexes. Loss of FPC from E3 ligases may alter the cellular proteome, contributing to cystogenesis through multiple, yet to be defined, mechanisms.\n                  <\/jats:p>","DOI":"10.1096\/fj.202300100r","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T11:25:05Z","timestamp":1686828305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cystin is required for maintaining fibrocystin (\n                    <scp>FPC<\/scp>\n                    ) levels and safeguarding proteome integrity in mouse renal epithelial cells"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8102-3815","authenticated-orcid":false,"given":"Yiming J.","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cell Developmental and Integrative Biology (CDIB) University of Alabama at Birmingham, School of Medicine  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5388-7173","authenticated-orcid":false,"given":"Chaozhe","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Translational Research Children's National Hospital  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5055-1229","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Research Center University of Alabama at Birmingham, School of Medicine  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7741-4549","authenticated-orcid":false,"given":"Naoe","family":"Harafuji","sequence":"additional","affiliation":[{"name":"Center for Translational Research Children's National Hospital  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Stasiak","sequence":"additional","affiliation":[{"name":"Department of Cell Developmental and Integrative Biology (CDIB) University of Alabama at Birmingham, School of Medicine  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Darwin","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9140-5585","authenticated-orcid":false,"given":"Ljubica","family":"Caldovic","sequence":"additional","affiliation":[{"name":"Center for Translational Research Children's National Hospital  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Sztul","sequence":"additional","affiliation":[{"name":"Department of Cell Developmental and Integrative Biology (CDIB) University of Alabama at Birmingham, School of Medicine  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-3927","authenticated-orcid":false,"given":"Lisa 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ARPKD"],"short-title":[],"issued":{"date-parts":[[2023,6,15]]},"references-count":90,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1096\/fj.202300100R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202300100r","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.04.19.488799","asserted-by":"object"}]},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,15]]},"assertion":[{"value":"2023-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication 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