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It has been suggested that proteins with expanded polyglutamine tracts impair ubiquitin-dependent proteolysis due to their propensity to aggregate, but recent studies indicate that the overall activity of the ubiquitin-proteasome system is preserved in SBMA models. Here we report that AR selectively interferes with the function of the ubiquitin ligase anaphase-promoting complex\/cyclosome (APC\/C), which, together with its substrate adaptor Cdh1, is critical for cell cycle arrest and neuronal architecture. We show that both wild-type and mutant AR physically interact with the APC\/C<jats:sup>Cdh1<\/jats:sup> complex in a ligand-dependent fashion without being targeted for proteasomal degradation. Inhibition of APC\/C<jats:sup>Cdh1<\/jats:sup> by mutant but not wild-type AR in PC12 cells results in enhanced neurite outgrowth which is typically followed by rapid neurite retraction and mitotic entry. Our data indicate a role of AR in neuronal differentiation through regulation of APC\/C<jats:sup>Cdh1<\/jats:sup> and suggest abnormal cell cycle reactivation as a pathogenic mechanism in SBMA.<\/jats:p>","DOI":"10.1038\/srep27703","type":"journal-article","created":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T08:58:42Z","timestamp":1466153922000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The polyglutamine-expanded androgen receptor responsible for spinal and bulbar muscular atrophy inhibits the APC\/CCdh1 ubiquitin ligase complex"],"prefix":"10.1038","volume":"6","author":[{"given":"Laura C.","family":"Bott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian A.","family":"Salomons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragan","family":"Maric","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Merry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth H.","family":"Fischbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico P.","family":"Dantuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,17]]},"reference":[{"key":"BFsrep27703_CR1","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1212\/WNL.18.7.671","volume":"18","author":"WR Kennedy","year":"1968","unstructured":"Kennedy, W. 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