Cited 44 times in

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  ;  Jie Wu  ;  Eun Sung Kim  ;  Min Kyung Kwon  ;  Man Sup Kwak  ;  Ji Eun Choi  ;  Jong Eun Lee  ;  Jeon-Soo Shin 
Citation
 JOURNAL OF IMMUNOLOGY, Vol.190(4) : 1797-1806, 2013 
Journal Title
JOURNAL OF IMMUNOLOGY
ISSN
 0022-1767 
Issue Date
2013
MeSH
Animals ; Cell Line ; Cell Line, Tumor ; Cells, Cultured ; Cricetinae ; Cricetulus ; HEK293 Cells ; HMGB1 Protein/deficiency ; HMGB1 Protein/metabolism ; HMGB1 Protein/physiology* ; Humans ; Mice ; Mice, Knockout ; Molecular Chaperones/chemistry ; Molecular Chaperones/metabolism* ; Molecular Chaperones/physiology ; NIH 3T3 Cells ; Neuroblastoma/metabolism ; Neuroblastoma/therapy ; Peptides/antagonists & inhibitors* ; Peptides/metabolism*
Keywords
Animals ; Cell Line ; Cell Line, Tumor ; Cells, Cultured ; Cricetinae ; Cricetulus ; HEK293 Cells ; HMGB1 Protein/deficiency ; HMGB1 Protein/metabolism ; HMGB1 Protein/physiology* ; Humans ; Mice ; Mice, Knockout ; Molecular Chaperones/chemistry ; Molecular Chaperones/metabolism* ; Molecular Chaperones/physiology ; NIH 3T3 Cells ; Neuroblastoma/metabolism ; Neuroblastoma/therapy ; Peptides/antagonists & inhibitors* ; Peptides/metabolism*
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.
Full Text
http://www.jimmunol.org/content/190/4/1797.long
DOI
10.4049/jimmunol.1202472
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kwak, Man Sup(곽만섭) ORCID logo https://orcid.org/0000-0002-3989-3016
Min, Hyun Jin(민현진)
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86229
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links