Back to Search Start Over

A key lysine residue in the AXH domain of ataxin-1 is essential for its ubiquitylation

Authors :
Seongman Kang
Aram Kang
Si Hoon Park
Kwang Pyo Kim
Sunghoi Hong
Soyeon Lee
Do-Young Choi
Hyun Kyu Song
Source :
Biochimica et biophysica acta. 1854(5)
Publication Year :
2014

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.

Details

ISSN :
00063002
Volume :
1854
Issue :
5
Database :
OpenAIRE
Journal :
Biochimica et biophysica acta
Accession number :
edsair.doi.dedup.....69b7e9a7933c53220ed919ce105e0329