{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:53:14Z","timestamp":1791204794824,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T00:00:00Z","timestamp":1515542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T00:00:00Z","timestamp":1515542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>\n                    Autosomal\u2010dominant polycystic kidney disease (ADPKD) is associated with progressive formation of renal cysts, kidney enlargement, hypertension, and typically end\u2010stage renal disease. In ADPKD, inherited mutations disrupt function of the polycystins (encoded by\n                    <jats:italic>PKD1<\/jats:italic>\n                    and\n                    <jats:italic>PKD2),<\/jats:italic>\n                    thus causing loss of a cyst\u2010repressive signal emanating from the renal cilium. Genetic studies have suggested ciliary maintenance is essential for ADPKD pathogenesis. Heat shock protein 90 (HSP90) clients include multiple proteins linked to ciliary maintenance. We determined that ganetespib, a clinical HSP90 inhibitor, inhibited proteasomal repression of NEK8 and the Aurora\u2010A activator trichoplein, rapidly activating Aurora\u2010A kinase and causing ciliary loss\n                    <jats:italic>in vitro.<\/jats:italic>\n                    Using conditional mouse models for ADPKD, we performed long\u2010term (10 or 50 wk) dosing experiments that demonstrated HSP90 inhibition caused durable\n                    <jats:italic>in vivo<\/jats:italic>\n                    loss of cilia, controlled cystic growth, and ameliorated symptoms induced by loss of\n                    <jats:italic>Pkd1<\/jats:italic>\n                    or\n                    <jats:italic>Pkd<\/jats:italic>\n                    2. Ganetespib efficacy was not increased by combination with 2\u2010deoxy\u2010D\u2010glucose, a glycolysis inhibitor showing some promise for ADPKD. These studies identify a new biologic activity for HSP90 and support a cilia\u2010based mechanism for cyst repression.\u2014Nikonova, A. S., Deneka, A. Y., Kiseleva, A. A., Korben, V.A., Gaponova, A., Serebriiskii, I. G., Kopp, M. C., Hensley, H. H., Seeger\u2010Nukpezah, T. N., Somlo, S., Proia, D. A., Golemis, E. A. Ganetespib limits ciliation and cystogenesis in autosomal\u2010dominant polycystic kidney disease (ADPKD). FASEB J. 32, 2735\u20132746 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700909r","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T14:33:21Z","timestamp":1516890801000},"page":"2735-2746","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Ganetespib limits ciliation and cystogenesis in autosomal\u2010dominant polycystic kidney disease (ADPKD)"],"prefix":"10.1096","volume":"32","author":[{"given":"Anna S.","family":"Nikonova","sequence":"first","affiliation":[{"name":"Institute for Cancer Research Fox Chase Cancer Center Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Y.","family":"Deneka","sequence":"additional","affiliation":[{"name":"Institute for 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