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Here we identify a new interplay between the PKD and TSC genes, with important implications for the pathophysiology of both diseases. Kidney-specific inactivation of either\n                    <jats:italic>Pkd1<\/jats:italic>\n                    or\n                    <jats:italic>Tsc1<\/jats:italic>\n                    using an identical Cre (\n                    <jats:italic>KspCre<\/jats:italic>\n                    ) results in aggressive or very mild PKD, respectively. Unexpectedly, we find that mTORC1 negatively regulates the biogenesis of polycystin-1 (PC-1) and trafficking of the PC-1\/2 complex to cilia. Genetic interaction studies reveal an important role for PC-1 downregulation by mTORC1 in the cystogenesis of\n                    <jats:italic>Tsc1<\/jats:italic>\n                    mutants. Our data potentially explain the severe renal manifestations of the TSC\/PKD contiguous gene syndrome and open new perspectives for the use of mTOR inhibitors in autosomal dominant PKD caused by hypomorphic or missense\n                    <jats:italic>PKD1<\/jats:italic>\n                    mutations.\n                  <\/jats:p>","DOI":"10.1038\/ncomms10786","type":"journal-article","created":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T06:40:56Z","timestamp":1456900856000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["mTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complex"],"prefix":"10.1038","volume":"7","author":[{"given":"Monika","family":"Pema","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Drusian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Chiaravalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Castelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ricciardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Somlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Biffo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Boletta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,2]]},"reference":[{"key":"BFncomms10786_CR1","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1146\/annurev.med.60.101707.125712","volume":"60","author":"PC Harris","year":"2009","unstructured":"Harris, P. 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