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Using N\u2010terminal huntingtin (Htt\u2010N552) and ataxin (Atx)\u20103 as model proteins, we investigated the molecular mechanism underlying sequestration of Ub adaptors by polyQ\u2010expanded proteins. We found that polyQ\u2010expanded Htt\u2010N552 and Atx\u20103 sequester endogenous Ub adaptors, human RAD23 homolog B (hHR23B) and ubiquilin (UBQLN)\u20102, into inclusions. This sequestration effect is dependent on the UBA domains of Ub adaptors and the conjugated Ub of the aggregated proteins. Moreover, polyQ\u2010expanded Htt\u2010N552 and Atx\u20103 reduce the protein level of xeroderma pigmentosum group C (XPC) by sequestration of hHR23B, suggesting that this process may cut down the available quantity of hHR23B and thus affect its normal function in stabilizing XPC. Our findings demonstrate that polyQ\u2010expanded proteins sequester Ub adaptors or other Ub\u2010related proteins into aggregates or inclusions through ubiquitination of the pathogenic proteins. This study may also provide a common mechanism for the formation of Ub\u2010positive inclusions in cells.\u2014Yang, H., Yue, H.\u2010W., He, W.\u2010T., Hong, J.\u2010Y., Jiang, L.\u2010L., Hu, H.\u2010Y. PolyQ\u2010expanded huntingtin and ataxin\u20103 sequester ubiquitin adaptors hHR23B and UBQLN2 into aggregates\n                    <jats:italic>via<\/jats:italic>\n                    conjugated ubiquitin. FASEB J. 32, 2923\u20132933 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700801rr","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T14:33:21Z","timestamp":1516890801000},"page":"2923-2933","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["PolyQ\u2010expanded huntingtin and ataxin\u20103 sequester ubiquitin adaptors hHR23B and UBQLN2 into aggregates\n                    <i>via<\/i>\n                    conjugated ubiquitin"],"prefix":"10.1096","volume":"32","author":[{"given":"Hui","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Biology Chinese Academy of Sciences (CAS) Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell 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