Chaperone-like activity of high-mobility group box 1 protein and its role in reducing the formation of polyglutamine aggregates

Hyun Jin Min, Eun Ae Ko, Jie Wu, Eun Sung Kim, Min Kyung Kwon, Man Sup Kwak, Ji Eun Choi, Jongeun Lee, Jeon Soo Shin

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1797-1806
Number of pages10
JournalJournal of Immunology
Volume190
Issue number4
DOIs
Publication statusPublished - 2013 Feb 15

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HMGB1 Protein
Fluorescent Antibody Technique
polyglutamine
Fibroblasts
Hot Temperature
Corpus Striatum
Citrate (si)-Synthase
Proteins
Huntington Disease
Autophagy
Muramidase
Luciferases
Cricetinae
Nucleic Acids
Cytoplasm

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Min, Hyun Jin ; Ko, Eun Ae ; Wu, Jie ; Kim, Eun Sung ; Kwon, Min Kyung ; Kwak, Man Sup ; Choi, Ji Eun ; Lee, Jongeun ; Shin, Jeon Soo. / Chaperone-like activity of high-mobility group box 1 protein and its role in reducing the formation of polyglutamine aggregates. In: Journal of Immunology. 2013 ; Vol. 190, No. 4. pp. 1797-1806.
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Chaperone-like activity of high-mobility group box 1 protein and its role in reducing the formation of polyglutamine aggregates. / Min, Hyun Jin; Ko, Eun Ae; Wu, Jie; Kim, Eun Sung; Kwon, Min Kyung; Kwak, Man Sup; Choi, Ji Eun; Lee, Jongeun; Shin, Jeon Soo.

In: Journal of Immunology, Vol. 190, No. 4, 15.02.2013, p. 1797-1806.

Research output: Contribution to journalArticle

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