The proinflammatory protein HMGB1 is a substrate of transglutaminase-2 and forms high-molecular weight complexes with autoantigens.

Autor:	Willis WL; From the Departments of Internal Medicine, william.willis@osumc.edu.; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210., Wang L; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210.; Cancer Biology and Genetics, and., Wada TT; From the Departments of Internal Medicine.; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210., Gardner M; From the Departments of Internal Medicine.; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210., Abdouni O; From the Departments of Internal Medicine.; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210., Hampton J; From the Departments of Internal Medicine.; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210., Valiente G; From the Departments of Internal Medicine.; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210., Young N; From the Departments of Internal Medicine.; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210., Ardoin S; From the Departments of Internal Medicine.; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210., Agarwal S; Division of Biosciences, The Ohio State University College of Dentistry, Columbus, Ohio 43210.; the Department of Orthopedics, The Ohio State University College of Medicine, Columbus, Ohio 43210, and., Freitas MA; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210.; Cancer Biology and Genetics, and., Wu LC; From the Departments of Internal Medicine.; Biological Chemistry and Pharmacology and., Jarjour WN; From the Departments of Internal Medicine, wael.jarjour@osumc.edu.; The Ohio State University Wexner Medical Center, Columbus, Ohio 43210.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2018 Jun 01; Vol. 293 (22), pp. 8394-8409. Date of Electronic Publication: 2018 Apr 04.
DOI:	10.1074/jbc.RA117.001078
Abstrakt:	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. (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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