1. Endoplasmic reticulum chaperone GRP78 suppresses the aggregation of proteins containing expanded polyglutamine tract.
- Author
-
Yamagishi N, Magara S, Tamura S, Saito Y, and Hatayama T
- Subjects
- Endoplasmic Reticulum Chaperone BiP, Gene Knockdown Techniques, Green Fluorescent Proteins metabolism, HeLa Cells, Heat-Shock Proteins genetics, Humans, Proteasome Endopeptidase Complex metabolism, Proteolysis, Ubiquitin metabolism, Endoplasmic Reticulum metabolism, Heat-Shock Proteins metabolism, Peptides metabolism
- Abstract
Polyglutamine (polyQ) diseases are inherited neurodegenerative diseases characterized by the aggregation of proteins containing expanded polyQ tract. It has been shown that expanded polyQ tract-containing proteins impair the functions of other cellular proteins. However, quantitative changes of cellular proteins in cells expressing expanded polyQ tract-containing proteins have not been performed. Here, we performed proteomic analysis of cells expressing expanded polyQ tract-containing proteins, and showed that GRP78, the endoplasmic reticulum (ER) chaperone, was significantly decreased in the cells expressing enhanced green fluorescent protein with a pathological-length polyQ tract (EGFP-polyQ97), but not with a non-pathological-length polyQ tract (EGFP-polyQ24). In addition, we revealed that down-regulation of GRP78 expression resulted in increase of the aggregation of EGFP-polyQ97. Conversely, the aggregation of EGFP-polyQ97 was suppressed by the overexpression of GRP78 in the cells. Furthermore, it seemed that the decreased GRP78 expression in the cells expressing EGFP-polyQ97 was due to the enhanced protein degradation of GRP78 through the ubiquitin-proteasome pathway. These findings indicated that GRP78, which has an inhibitory effect on the aggregation of proteins containing expanded polyQ tract, may be an effective target for the treatment of polyQ diseases., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF