Proteasome function is inhibited by polyglutamine-expanded ataxin-1, the SCA1 gene product

Yongjae Park, Sunghoi Hong, Sung Jo Kim, Seongman Kang

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39 Citations (Scopus)


Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder caused by expansion of the polyglutamine tract in the SCA1 gene product, ataxin-1. Using d2EGFP, a short-lived enhanced green fluorescent protein, we investigated whether polyglutamine-expanded ataxin-1 affects the function of the proteasome, a cellular multicatalytic protease that degrades most misfolded proteins and regulatory proteins. In Western blot analysis and immunofluorescence experiments, d2EGFP was less degraded in HEK 293T cells transfected with ataxin-1 (82Q) than in cells transfected with lacZ or empty vector controls. To test whether the stability of the d2EGFP protein was due to aggregation of ataxin-1, we constructed a plasmid carrying ataxin-1-Right Triangle Sign 114, lacking the self-association region (SAR), and examined degradation of the d2EGFP. Both the level of ataxin-1-Right Triangle Sign 114 aggregates and the amount of d2EGFP were drastically reduced in cells containing ataxin-1-Right Triangle Sign 114. Furthermore, d2EGFP localization experiments showed that polyglutamine-expanded ataxin-1 inhibited the general function of the proteasome activity. Taken together, these results demonstrate that polyglutamine-expanded ataxin-1 decreases the activity of the proteasome, implying that a disturbance in the ubiquitin-proteasome pathway is directly involved in the development of spinocerebellar ataxia type 1.

Original languageEnglish
Pages (from-to)23-30
Number of pages8
JournalMolecules and cells
Issue number1
Publication statusPublished - 2005


  • Ataxin-1
  • Polyglutamine
  • Proteasome
  • SAR
  • SCA1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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