{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T23:59:56Z","timestamp":1778975996634,"version":"3.51.4"},"reference-count":92,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS08677"],"award-info":[{"award-number":["R01NS08677"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006710","name":"Wayne State University","doi-asserted-by":"publisher","award":["Competitive Graduate Research Assistantship"],"award-info":[{"award-number":["Competitive Graduate Research Assistantship"]}],"id":[{"id":"10.13039\/100006710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Spinocerebellar ataxia type 3 (SCA3) belongs to the family of polyglutamine neurodegenerations. Each disorder stems from the abnormal lengthening of a glutamine repeat in a different protein. Although caused by a similar mutation, polyglutamine disorders are distinct, implicating non-polyglutamine regions of disease proteins as regulators of pathogenesis. SCA3 is caused by polyglutamine expansion in ataxin-3. To determine the role of ataxin-3\u2019s non-polyglutamine domains in disease, we utilized a new, allelic series of\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    . We found that ataxin-3 pathogenicity is saliently controlled by polyglutamine-adjacent ubiquitin-interacting motifs (UIMs) that enhance aggregation and toxicity. UIMs function by interacting with the heat shock protein, Hsc70-4, whose reduction diminishes ataxin-3 toxicity in a UIM-dependent manner. Hsc70-4 also enhances pathogenicity of other polyglutamine proteins. Our studies provide a unique insight into the impact of ataxin-3 domains in SCA3, identify Hsc70-4 as a SCA3 enhancer, and indicate pleiotropic effects from HSP70 chaperones, which are generally thought to suppress polyglutamine degeneration.\n                  <\/jats:p>","DOI":"10.7554\/elife.60742","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T06:00:27Z","timestamp":1600668027000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.60742","source":"Crossref","is-referenced-by-count":24,"title":["Ubiquitin-interacting motifs of ataxin-3 regulate its polyglutamine toxicity through Hsc70-4-dependent aggregation"],"prefix":"10.7554","volume":"9","author":[{"given":"Sean L","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Wayne State University, Detroit, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2508-731X","authenticated-orcid":true,"given":"Bedri","family":"Ranxhi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wayne State University, Detroit, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kozeta","family":"Libohova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wayne State University, Detroit, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ling","family":"Tsou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wayne State University, Detroit, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4399-5549","authenticated-orcid":true,"given":"Sokol V","family":"Todi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wayne State University, 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