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Mol. Cells 2005; 19(1): 23-30

Published online February 28, 2005

© The Korean Society for Molecular and Cellular Biology

Proteasome Function Is Inhibited by Polyglutamine-expanded Ataxin-1, the SCA1 Gene Product

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

Abstract

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-Δ114, lacking the self-association region (SAR), and examined degradation of the d2EGFP. Both the level of ataxin-1-Δ114 aggregates and the amount of d2EGFP were drastically reduced in cells containing ataxin-1-Δ114. 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 type1.

Keywords Ataxin-1, Polyglutamine, Proteasome, SAR, SCA1.

Article

Research Article

Mol. Cells 2005; 19(1): 23-30

Published online February 28, 2005

Copyright © The Korean Society for Molecular and Cellular Biology.

Proteasome Function Is Inhibited by Polyglutamine-expanded Ataxin-1, the SCA1 Gene Product

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

Abstract

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-Δ114, lacking the self-association region (SAR), and examined degradation of the d2EGFP. Both the level of ataxin-1-Δ114 aggregates and the amount of d2EGFP were drastically reduced in cells containing ataxin-1-Δ114. 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 type1.

Keywords: Ataxin-1, Polyglutamine, Proteasome, SAR, SCA1.

Mol. Cells
May 31, 2022 Vol.45 No.5, pp. 273~352
COVER PICTURE
Fe2+ ion depletion-induced expression of BΔGFP at the early stage of leaf development (Choi et al., pp. 294-305).

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