{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:47:47Z","timestamp":1768506467830,"version":"3.49.0"},"posted":{"date-parts":[[2023,6,1]]},"group-title":"Neuroscience","reference-count":44,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Ataxin-3 (Atxn3) is a deubiquitinase with a polyglutamine (polyQ) repeat tract whose abnormal expansion causes the neurodegenerative disease, Spinocerebellar Ataxia Type 3 (SCA3; also known as Machado-Joseph Disease). The ubiquitin chain cleavage properties of Atxn3 are enhanced when it is ubiquitinated at lysine (K) at position 117. K117-ubiqutinated Atxn3 cleaves poly-ubiquitin more rapidly in vitro compared to its unmodified counterpart and this residue is also important for Atxn3 roles in cell culture and in\n                  <jats:italic>Drosophila melanogaster<\/jats:italic>\n                  . How polyQ expansion causes SCA3 remains unclear. To gather insight into the biology of disease of SCA3, here we posited the question: is K117 important for toxicity caused by Atxn3? We generated transgenic\n                  <jats:italic>Drosophila<\/jats:italic>\n                  lines that express full-length, human, pathogenic Atxn3 with 80 polyQ with an intact or mutated K117. We found that K117 mutation mildly enhances the toxicity and aggregation of pathogenic Atxn3 in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  . An additional transgenic line that expresses Atxn3 without any K residues confirms increased aggregation of pathogenic Atxn3 whose ubiquitination is perturbed. These findings suggest Atxn3 ubiquitination as a regulatory step of SCA3, in part by modulating its aggregation.\n                <\/jats:p>","DOI":"10.1101\/2023.05.30.542896","type":"posted-content","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T13:25:24Z","timestamp":1685625924000},"source":"Crossref","is-referenced-by-count":0,"title":["Lysine 117 on ataxin-3 modulates toxicity in\n                  <i>Drosophila<\/i>\n                  models of Spinocerebellar Ataxia Type 3"],"prefix":"10.64898","author":[{"given":"Jessica R.","family":"Blount","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikhil C.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kozeta","family":"Libohova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Autumn L.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ling","family":"Tsou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9909-9279","authenticated-orcid":false,"given":"Alyson","family":"Sujkowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4399-5549","authenticated-orcid":false,"given":"Sokol V.","family":"Todi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023060507300880000_2023.05.30.542896v1.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4540-06.2007"},{"key":"2023060507300880000_2023.05.30.542896v1.2","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1002\/jnr.24684","article-title":"Degron capability of the hydrophobic C-terminus of the polyglutamine disease protein, ataxin-3","volume":"98","year":"2020","journal-title":"Journal of Neuroscience Research"},{"key":"2023060507300880000_2023.05.30.542896v1.3","doi-asserted-by":"crossref","unstructured":"Blount, J. R. , et al., 2014. Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23. Nature Communications. 5.","DOI":"10.1038\/ncomms5638"},{"key":"2023060507300880000_2023.05.30.542896v1.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407252102"},{"key":"2023060507300880000_2023.05.30.542896v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-38266-7_10"},{"key":"2023060507300880000_2023.05.30.542896v1.6","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.fob.2013.10.005","article-title":"Enzymatic production of mono-ubiquitinated proteins for structural studies: The example of the Josephin domain of ataxin-3","volume":"3","year":"2013","journal-title":"Febs Open Bio"},{"key":"2023060507300880000_2023.05.30.542896v1.7","doi-asserted-by":"crossref","unstructured":"Faggiano, S. , et al., 2015. Allosteric regulation of deubiquitylase activity through ubiquitination. 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