Proteasome degrades soluble expanded polyglutamine completely and efficiently
To date, nine progressive neurodegenerative diseases are caused by expansion of the CAG repeat coding for polyglutamine, including Huntington's disease and several forms of spinocerebellar ataxia. Expanded polyglutamine causes dominant toxic gain-of-function related to its ability to aggregate....
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2004-06-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996104000191 |
| _version_ | 1818616202240458752 |
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| author | Andrej Michalik Christine Van Broeckhoven |
| author_facet | Andrej Michalik Christine Van Broeckhoven |
| author_sort | Andrej Michalik |
| collection | DOAJ |
| description | To date, nine progressive neurodegenerative diseases are caused by expansion of the CAG repeat coding for polyglutamine, including Huntington's disease and several forms of spinocerebellar ataxia. Expanded polyglutamine causes dominant toxic gain-of-function related to its ability to aggregate. Polyglutamine aggregates inhibit the proteasome, suggesting that reduced degradation of misfolded proteins might contribute to polyglutamine toxicity. Moreover, several observations indicate that soluble proteins harboring expanded polyglutamine display altered turnover. To examine whether soluble polyglutamine interfered with proteasome-mediated degradation, we analyzed degradation of model proteasome substrates carrying either 103 or 25 glutamines in transfected cells. Expanded and normal size polyglutamine were degraded to completion and with similar efficiency. Moreover, targeting of expanded polyglutamine for proteasome-mediated degradation did not compromise proteasome activity. Thus, we propose that polyglutamine-containing disease proteins can be readily digested by the proteasome if they carried a degradation signal. |
| first_indexed | 2024-12-16T16:46:03Z |
| format | Article |
| id | doaj.art-83b8818bcaf447beb818eeadcd3aa6f8 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T16:46:03Z |
| publishDate | 2004-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-83b8818bcaf447beb818eeadcd3aa6f82022-12-21T22:24:11ZengElsevierNeurobiology of Disease1095-953X2004-06-01161202211Proteasome degrades soluble expanded polyglutamine completely and efficientlyAndrej Michalik0Christine Van Broeckhoven1Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UIA), Antwerpen, BelgiumDepartment of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UIA), Antwerpen, BelgiumTo date, nine progressive neurodegenerative diseases are caused by expansion of the CAG repeat coding for polyglutamine, including Huntington's disease and several forms of spinocerebellar ataxia. Expanded polyglutamine causes dominant toxic gain-of-function related to its ability to aggregate. Polyglutamine aggregates inhibit the proteasome, suggesting that reduced degradation of misfolded proteins might contribute to polyglutamine toxicity. Moreover, several observations indicate that soluble proteins harboring expanded polyglutamine display altered turnover. To examine whether soluble polyglutamine interfered with proteasome-mediated degradation, we analyzed degradation of model proteasome substrates carrying either 103 or 25 glutamines in transfected cells. Expanded and normal size polyglutamine were degraded to completion and with similar efficiency. Moreover, targeting of expanded polyglutamine for proteasome-mediated degradation did not compromise proteasome activity. Thus, we propose that polyglutamine-containing disease proteins can be readily digested by the proteasome if they carried a degradation signal.http://www.sciencedirect.com/science/article/pii/S0969996104000191PolyglutaminePolyglutamine degradationProteasome |
| spellingShingle | Andrej Michalik Christine Van Broeckhoven Proteasome degrades soluble expanded polyglutamine completely and efficiently Neurobiology of Disease Polyglutamine Polyglutamine degradation Proteasome |
| title | Proteasome degrades soluble expanded polyglutamine completely and efficiently |
| title_full | Proteasome degrades soluble expanded polyglutamine completely and efficiently |
| title_fullStr | Proteasome degrades soluble expanded polyglutamine completely and efficiently |
| title_full_unstemmed | Proteasome degrades soluble expanded polyglutamine completely and efficiently |
| title_short | Proteasome degrades soluble expanded polyglutamine completely and efficiently |
| title_sort | proteasome degrades soluble expanded polyglutamine completely and efficiently |
| topic | Polyglutamine Polyglutamine degradation Proteasome |
| url | http://www.sciencedirect.com/science/article/pii/S0969996104000191 |
| work_keys_str_mv | AT andrejmichalik proteasomedegradessolubleexpandedpolyglutaminecompletelyandefficiently AT christinevanbroeckhoven proteasomedegradessolubleexpandedpolyglutaminecompletelyandefficiently |