{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T10:47:15Z","timestamp":1761821235392},"reference-count":62,"publisher":"Walter de Gruyter GmbH","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Several neurodegenerative diseases, including Kennedy's disease (KD), are associated with misfolding and aggregation of polyglutamine (polyQ)-expansion proteins. KD is caused by a polyQ-expansion in the androgen receptor (AR), a key player in male sexual differentiation. Interestingly, KD patients often show signs of mild-to-moderate androgen insensitivity syndrome (AIS) resulting from AR dysfunction. Here, we used the yeast <jats:italic>Saccharomyces cerevisiae<\/jats:italic> to investigate the molecular mechanism behind AIS in KD. Upon expression in yeast, polyQ-expanded N-terminal fragments of AR lacking the hormone binding domain caused a polyQ length-dependent growth defect. Interestingly, while AR fragments with 67 Q formed large, SDS-resistant inclusions, the most pronounced toxicity was observed upon expression of 102 Q fragments which accumulated exclusively as soluble oligomers in the 100\u2013600\u00a0kDa range. Analysis using a hormone-dependent luciferase reporter revealed that full-length polyQ-expanded AR is fully functional in transactivation, but becomes inactivated in the presence of the corresponding polyQ-expanded N-terminal fragment. Furthermore, the greatest impairment of AR activity was observed upon interaction of full-length AR with soluble AR fragments. Taken together, our results suggest that soluble polyQ-containing fragments bind to full-length AR and inactivate it, thus providing insight into the mechanism behind AIS in KD and possibly other polyglutamine diseases, such as Huntington's disease.<\/jats:p>","DOI":"10.1515\/bc.2008.169","type":"journal-article","created":{"date-parts":[[2008,10,9]],"date-time":"2008-10-09T12:23:15Z","timestamp":1223554995000},"page":"1455-1466","source":"Crossref","is-referenced-by-count":8,"title":["N-terminal polyglutamine-containing fragments inhibit androgen receptor transactivation function"],"prefix":"10.1515","volume":"389","author":[{"given":"Niclas W.","family":"Schiffer","sequence":"first","affiliation":[{"name":"Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jocelyn","family":"C\u00e9raline","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Strasbourg-Facult\u00e9 de M\u00e9decine, EA 3430-Signalisation et Cancer de la Prostate, F-67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. Ulrich","family":"Hartl","sequence":"additional","affiliation":[{"name":"Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah A.","family":"Broadley","sequence":"additional","affiliation":[{"name":"Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2008,10,9]]},"reference":[{"key":"p_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh381"},{"key":"p_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2007.00830.x"},{"key":"p_3","doi-asserted-by":"publisher","DOI":"10.1038\/nature02998"},{"key":"p_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2003.12.010"},{"key":"p_5","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.08.017"},{"key":"p_6","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(01)00466-X"},{"key":"p_7","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1997.0126"},{"key":"p_8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303354200"},{"key":"p_9","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.1.121"},{"key":"p_10","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1480099"},{"key":"p_11","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.15.3181"},{"key":"p_12","doi-asserted-by":"publisher","DOI":"10.1126\/science.7754373"},{"key":"p_13","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg151"},{"key":"p_14","doi-asserted-by":"publisher","DOI":"10.1007\/BF00190748"},{"key":"p_15","doi-asserted-by":"publisher","DOI":"10.1210\/jc.87.8.3893"},{"key":"p_16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604547103"},{"key":"p_17","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0720185.x"},{"key":"p_18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1176\/jnp.6.2.147","volume":"6","author":"Fedoroff J.P.","year":"1994","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"p_19","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0061(199707)13:9<837::AID-YEA145>3.0.CO;2-T"},{"key":"p_20","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1691"},{"key":"p_21","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.10.018"},{"key":"p_22","doi-asserted-by":"publisher","DOI":"10.1038\/ng1542"},{"key":"p_23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.29.20229"},{"key":"p_24","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.2.267"},{"key":"p_25","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.4.523"},{"key":"p_26","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9624"},{"key":"p_27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1589"},{"key":"p_28","doi-asserted-by":"publisher","DOI":"10.1002\/yea.1024"},{"key":"p_29","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440216"},{"key":"p_30","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S0002-9440(10)65612-X","volume":"153","author":"Li M.","year":"1998","journal-title":"Am. J. Pathol."},{"key":"p_31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609972200"},{"key":"p_32","doi-asserted-by":"publisher","DOI":"10.1038\/nature06731"},{"key":"p_33","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.2.508"},{"key":"p_34","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00501-4"},{"key":"p_35","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81369-0"},{"key":"p_36","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200112104"},{"key":"p_37","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.4.693"},{"key":"p_38","doi-asserted-by":"publisher","DOI":"10.1038\/ng1093-184"},{"key":"p_39","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-8-1-1"},{"key":"p_40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.140202897"},{"key":"p_41","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.25.5767"},{"key":"p_42","first-page":"456","volume":"15","author":"Pinsky L.","year":"1992","journal-title":"Clin. Invest. Med."},{"key":"p_43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205809200"},{"key":"p_44","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2004.03.001"},{"key":"p_45","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)61620-9"},{"key":"p_47","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.5.813"},{"key":"p_48","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.06.029"},{"key":"p_49","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80514-0"},{"key":"p_50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M607865200"},{"key":"p_51","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/genetics\/122.1.19","volume":"122","author":"Sikorski R.S.","year":"1989","journal-title":"Genetics"},{"key":"p_52","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(04)00082-0"},{"key":"p_53","doi-asserted-by":"publisher","DOI":"10.1038\/ng1193-259"},{"key":"p_54","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310226200"},{"key":"p_55","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg074"},{"key":"p_56","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl148"},{"key":"p_57","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.11.3777"},{"key":"p_58","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi147"},{"key":"p_59","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl072"},{"key":"p_60","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.01.006"},{"key":"p_61","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1212\/WNL.42.11.2181","volume":"42","author":"Warner C.L.","year":"1992","journal-title":"Neurology"},{"key":"p_62","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.15.9158"},{"key":"p_63","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090389"}],"container-title":["bchm"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.degruyter.com\/view\/j\/bchm.2008.389.issue-12\/bc.2008.169\/bc.2008.169.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/BC.2008.169\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/BC.2008.169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T10:04:09Z","timestamp":1653559449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/BC.2008.169\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,9]]},"references-count":62,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2008,10,9]]},"published-print":{"date-parts":[[2008,12,1]]}},"alternative-id":["10.1515\/BC.2008.169"],"URL":"https:\/\/doi.org\/10.1515\/bc.2008.169","relation":{},"ISSN":["1437-4315","1431-6730"],"issn-type":[{"value":"1437-4315","type":"electronic"},{"value":"1431-6730","type":"print"}],"subject":[],"published":{"date-parts":[[2008,10,9]]}}}