| Literature DB >> 25641559 |
A-ram Kang1, Si Hoon Park1, Soyeon Lee1, Do-Young Choi2, Kwang Pyo Kim2, Hyun Kyu Song1, Sunghoi Hong3, Seongman Kang4.
Abstract
Spinocerebellar ataxia type 1 (SCA1), an autosomal-dominant neurodegenerative disorder, is caused by expansion of the polyglutamine tract within ataxin-1 (ATXN1). The AXH domain of ATXN1 can mediate neurodegeneration through its interaction with other proteins. We have previously showed that the ubiquitin-conjugating enzyme UbcH6 modulates the transcriptional repression activity of ATXN1 through ubiquitylation. In the present study, we sought to identify sites in the AXH domain that are ubiquitylated by UbcH6. Systematic replacement of each lysine residue in the AXH domain revealed that the lysine at 589 (K589) of ATXN1 is essential for its ubiquitylation by UbcH6. Mass spectrometry studies further confirmed the ubiquitylation site. Interestingly, protein aggregation was significantly enhanced in mutant AXH K589R, implying that the aggregation is strongly associated with the level of ATXN1 expression. Our study may suggest a therapeutic potential of UbcH6 in the treatment of SCA1.Entities:
Keywords: Ataxin-1; Protein aggregation; Protein degradation; Spinocerebellar ataxia type 1 (SCA1); UbcH6; Ubiquitylation
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Year: 2015 PMID： 25641559 DOI： 10.1016/j.bbapap.2015.01.012
Source DB: PubMed Journal: Biochim Biophys Acta ISSN： 0006-3002