The proinflammatory protein HMGB1 is a substrate of transglutaminase-2 and forms high-molecular weight complexes with autoantigens.
J Biol Chem
; 293(22): 8394-8409, 2018 06 01.
Article
em En
| MEDLINE
| ID: mdl-29618516
ABSTRACT
High-mobility group box 1 (HMGB1) is a chromatin-associated protein that, in response to stress or injury, translocates from the nucleus to the extracellular milieu, where it functions as an alarmin. HMGB1's function is in part determined by the complexes (HMGB1c) it forms with other molecules. However, structural modifications in the HMGB1 polypeptide that may regulate HMGB1c formation have not been previously described. In this report, we observed high-molecular weight, denaturing-resistant HMGB1c in the plasma and peripheral blood mononuclear cells of individuals with systemic lupus erythematosus (SLE) and, to a much lesser extent, in healthy subjects. Differential HMGB1c levels were also detected in mouse tissues and cultured cells, in which these complexes were induced by endotoxin or the immunological adjuvant alum. Of note, we found that HMGB1c formation is catalyzed by the protein-cross-linking enzyme transglutaminase-2 (TG2). Cross-link site mapping and MS analysis revealed that HMGB1 can be cross-linked to TG2 as well as a number of additional proteins, including human autoantigens. These findings have significant functional implications for studies of cellular stress responses and innate immunity in SLE and other autoimmune disease.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
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Leucócitos Mononucleares
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Transglutaminases
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Proteínas de Ligação ao GTP
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Proteína HMGB1
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Lúpus Eritematoso Sistêmico
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article