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The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are still poorly understood. Here, we show that in\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    Cdk5 regulates basal autophagy, a key mechanism suppressing neurodegeneration. In a targeted screen, Cdk5 genetically interacted with Acinus (Acn), a primarily nuclear protein, which promotes starvation-independent, basal autophagy. Loss of Cdk5, or its required cofactor p35, reduces S437-Acn phosphorylation, whereas Cdk5 gain-of-function increases pS437-Acn levels. The phospho-mimetic S437D mutation stabilizes Acn and promotes basal autophagy. In\n                    <jats:italic>p35<\/jats:italic>\n                    mutants, basal autophagy and lifespan are reduced, but restored to near wild-type levels in the presence of stabilized Acn\n                    <jats:sup>S437D<\/jats:sup>\n                    . Expression of aggregation-prone polyQ-containing proteins or the Amyloid-\u03b242 peptide, but not alpha-Synuclein, enhances Cdk5-dependent phosphorylation of S437-Acn. Our data indicate that Cdk5 is required to maintain the protective role of basal autophagy in the initial responses to a subset of neurodegenerative challenges.\n                  <\/jats:p>","DOI":"10.7554\/elife.30760","type":"journal-article","created":{"date-parts":[[2017,12,11]],"date-time":"2017-12-11T08:00:15Z","timestamp":1512979215000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.30760","source":"Crossref","is-referenced-by-count":34,"title":["Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-4943","authenticated-orcid":true,"given":"Nilay","family":"Nandi","sequence":"first","affiliation":[{"name":"Department of Neuroscience, UT Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren 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