title: Chaperone-like activity of high-mobility group box 1 protein and its role in reducing the formation of polyglutamine aggregates.
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.
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Min
authors.forename: Eun Ae
authors.initials: EA
authors.lastname: Ko
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Eun Sung
authors.initials: ES
authors.lastname: Kim
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Kwon
authors.forename: Man Sup
authors.initials: MS
authors.lastname: Kwak
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Jeon-Soo
authors.initials: JS
authors.lastname: Shin
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D057809:HEK293 Cells; D024243:HMGB1 Protein / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D041681:NIH 3T3 Cells; D009447:Neuroblastoma / Q000378:metabolism / Q000628:therapy; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; D018832:Molecular Chaperones; D010455:Peptides; C097188:polyglutamine