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Chaperone-like Activity of High-Mobility Group Box 1 Protein and Its Role in Reducing the Formation of Polyglutamine Aggregates

Title
 Chaperone-like Activity of High-Mobility Group Box 1 Protein and Its Role in Reducing the Formation of Polyglutamine Aggregates
Authors
 Hyun Jin Min; Eun Ae Ko; Jeon-Soo Shin; Jong Eun Lee; Ji Eun Choi; Man Sup Kwak; Min Kyung Kwon; Eun Sung Kim; Jie Wu
Issue Date
2013
Journal Title
 Journal of Immunology
ISSN
 0022-1767
Citation
 Journal of Immunology, Vol.190(4) : 1797~1806, 2013
Abstract
High-mobility group box 1 protein (HMGB1), which mainly exists in the nucleus, has recently been shown to function as a sentinel molecule for viral nucleic acid sensing and an autophagy regulator in the cytoplasm. In this study, we studied the chaperone-like activity of HMGB1 and found that HMGB1 inhibited the chemically induced aggregation of insulin and lysozyme, as well as the heat-induced aggregation of citrate synthase. HMGB1 also restored the heat-induced suppression of cytoplasmic luciferase activity as a reporter protein in hamster lung fibroblast O23 cells with expression of HMGB1. Next, we demonstrated that HMGB1 inhibited the formation of aggregates and toxicity caused by expanded polyglutamine (polyQ), one of the main causes of Huntington disease. HMGB1 directly interacted with polyQ on immunofluorescence and coimmunoprecipitation assay, whereas the overexpression of HMGB1 or exogenous administration of recombinant HMGB1 protein remarkably reduced polyQ aggregates in SHSY5Y cells and hmgb1−/− mouse embryonic fibroblasts upon filter trap and immunofluorescence assay. Finally, overexpressed HMGB1 proteins in mouse embryonic primary striatal neurons also bound to polyQ and decreased the formation of polyQ aggregates. To this end, we have demonstrated that HMGB1 exhibits chaperone-like activity and a possible therapeutic candidate in polyQ disease.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/86229
DOI
10.4049/jimmunol.1202472
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Microbiology
1. 연구논문 > 1. College of Medicine > Dept. of Anatomy
Yonsei Authors
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Link
 http://www.jimmunol.org/content/190/4/1797.long
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