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The polyglutamine-e...
The polyglutamine-expanded androgen receptor responsible for spinal and bulbar muscular atrophy inhibits the APC/C(Cdh1) ubiquitin ligase complex
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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2016-06-17
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Springer Science and Business Media LLC,2016
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:133768145
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http://kipublications.ki.se/Default.aspx?queryparsed=id:133768145URI
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https://doi.org/10.1038/srep27703DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Polyglutamine expansion in the androgen receptor (AR) causes spinal and bulbar muscular atrophy (SBMA), an X-linked neuromuscular disease that is fully manifest only in males. It has been suggested that proteins with expanded polyglutamine tracts impair ubiquitin-dependent proteolysis due to their propensity to aggregate, but recent studies indicate that the overall activity of the ubiquitin-proteasome system is preserved in SBMA models. Here we report that AR selectively interferes with the function of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), which, together with its substrate adaptor Cdh1, is critical for cell cycle arrest and neuronal architecture. We show that both wild-type and mutant AR physically interact with the APC/CCdh1 complex in a ligand-dependent fashion without being targeted for proteasomal degradation. Inhibition of APC/CCdh1 by mutant but not wild-type AR in PC12 cells results in enhanced neurite outgrowth which is typically followed by rapid neurite retraction and mitotic entry. Our data indicate a role of AR in neuronal differentiation through regulation of APC/CCdh1 and suggest abnormal cell cycle reactivation as a pathogenic mechanism in SBMA.
Added entries (persons, corporate bodies, meetings, titles ...)
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Salomons, FAKarolinska Institutet
(author)
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Maric, D
(author)
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Liu, YH
(author)
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Merry, D
(author)
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Fischbeck, KH
(author)
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Dantuma, NPKarolinska Institutet
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:Scientific reports: Springer Science and Business Media LLC6, s. 27703-2045-2322
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