Immunological Significance of HMGB1 Post-Translational Modification and Redox Biology
Most extracellular proteins are secreted via the classical endoplasmic reticulum (ER)/Golgi-dependent secretion pathway; however, some proteins, including a few danger-associated molecular patterns (DAMPs), are secreted via non-classical ER/Golgi-independent secretion pathways. The evolutionarily co...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01189/full |
| _version_ | 1819110781125394432 |
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| author | Man Sup Kwak Man Sup Kwak Hee Sue Kim Bin Lee Young Hun Kim Young Hun Kim Myoungsun Son Jeon-Soo Shin Jeon-Soo Shin Jeon-Soo Shin Jeon-Soo Shin |
| author_facet | Man Sup Kwak Man Sup Kwak Hee Sue Kim Bin Lee Young Hun Kim Young Hun Kim Myoungsun Son Jeon-Soo Shin Jeon-Soo Shin Jeon-Soo Shin Jeon-Soo Shin |
| author_sort | Man Sup Kwak |
| collection | DOAJ |
| description | Most extracellular proteins are secreted via the classical endoplasmic reticulum (ER)/Golgi-dependent secretion pathway; however, some proteins, including a few danger-associated molecular patterns (DAMPs), are secreted via non-classical ER/Golgi-independent secretion pathways. The evolutionarily conserved high mobility group box1 (HMGB1) is a ubiquitous nuclear protein that can be released by almost all cell types. HMGB1 lacks signal peptide and utilizes diverse non-canonical secretion mechanisms for its extracellular export. Although the post-translational modifications of HMGB1 were demonstrated, the oxidation of HMGB1 and secretion mechanisms are not highlighted yet. We currently investigated that peroxiredoxins I and II (PrxI/II) induce the intramolecular disulfide bond formation of HMGB1 in the nucleus. Disulfide HMGB1 is preferentially transported out of the nucleus by binding to the nuclear exportin chromosome-region maintenance 1 (CRM1). We determined the kinetics of HMGB1 oxidation in bone marrow-derived macrophage as early as a few minutes after lipopolysaccharide treatment, peaking at 4 h while disulfide HMGB1 accumulation was observed within the cells, starting to secrete in the late time point. We have shown that HMGB1 oxidation status, which is known to determine the biological activity in extracellular HMGB1, is crucial for the secretion of HMGB1 from the nucleus. This review summarizes selected aspects of HMGB1 redox biology relevant to the induction and propagation of inflammatory diseases. We implicate the immunological significance and the need for novel HMGB1 inhibitors through mechanism-based studies. |
| first_indexed | 2024-12-22T03:47:10Z |
| format | Article |
| id | doaj.art-f7db2b585332434cb0a8fd70b4345f36 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T03:47:10Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f7db2b585332434cb0a8fd70b4345f362022-12-21T18:40:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-06-011110.3389/fimmu.2020.01189543149Immunological Significance of HMGB1 Post-Translational Modification and Redox BiologyMan Sup Kwak0Man Sup Kwak1Hee Sue Kim2Bin Lee3Young Hun Kim4Young Hun Kim5Myoungsun Son6Jeon-Soo Shin7Jeon-Soo Shin8Jeon-Soo Shin9Jeon-Soo Shin10Department of Microbiology, Yonsei University College of Medicine, Seoul, South KoreaInstitute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South KoreaDepartment of Microbiology, Yonsei University College of Medicine, Seoul, South KoreaDepartment of Microbiology, Yonsei University College of Medicine, Seoul, South KoreaDepartment of Microbiology, Yonsei University College of Medicine, Seoul, South KoreaInstitute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South KoreaCenter for Autoimmune Musculoskeletal and Hematopoietic Diseases, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, United StatesDepartment of Microbiology, Yonsei University College of Medicine, Seoul, South KoreaInstitute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South KoreaSeverance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South KoreaCenter for Nanomedicine, Institute for Basic Science (IBS), Yonsei University, Seoul, South KoreaMost extracellular proteins are secreted via the classical endoplasmic reticulum (ER)/Golgi-dependent secretion pathway; however, some proteins, including a few danger-associated molecular patterns (DAMPs), are secreted via non-classical ER/Golgi-independent secretion pathways. The evolutionarily conserved high mobility group box1 (HMGB1) is a ubiquitous nuclear protein that can be released by almost all cell types. HMGB1 lacks signal peptide and utilizes diverse non-canonical secretion mechanisms for its extracellular export. Although the post-translational modifications of HMGB1 were demonstrated, the oxidation of HMGB1 and secretion mechanisms are not highlighted yet. We currently investigated that peroxiredoxins I and II (PrxI/II) induce the intramolecular disulfide bond formation of HMGB1 in the nucleus. Disulfide HMGB1 is preferentially transported out of the nucleus by binding to the nuclear exportin chromosome-region maintenance 1 (CRM1). We determined the kinetics of HMGB1 oxidation in bone marrow-derived macrophage as early as a few minutes after lipopolysaccharide treatment, peaking at 4 h while disulfide HMGB1 accumulation was observed within the cells, starting to secrete in the late time point. We have shown that HMGB1 oxidation status, which is known to determine the biological activity in extracellular HMGB1, is crucial for the secretion of HMGB1 from the nucleus. This review summarizes selected aspects of HMGB1 redox biology relevant to the induction and propagation of inflammatory diseases. We implicate the immunological significance and the need for novel HMGB1 inhibitors through mechanism-based studies.https://www.frontiersin.org/article/10.3389/fimmu.2020.01189/fullhigh mobility group box1 (HMGB1)oxidationinflammationtherapeutic targetdanger-associated molecular pattern (DAMP) |
| spellingShingle | Man Sup Kwak Man Sup Kwak Hee Sue Kim Bin Lee Young Hun Kim Young Hun Kim Myoungsun Son Jeon-Soo Shin Jeon-Soo Shin Jeon-Soo Shin Jeon-Soo Shin Immunological Significance of HMGB1 Post-Translational Modification and Redox Biology Frontiers in Immunology high mobility group box1 (HMGB1) oxidation inflammation therapeutic target danger-associated molecular pattern (DAMP) |
| title | Immunological Significance of HMGB1 Post-Translational Modification and Redox Biology |
| title_full | Immunological Significance of HMGB1 Post-Translational Modification and Redox Biology |
| title_fullStr | Immunological Significance of HMGB1 Post-Translational Modification and Redox Biology |
| title_full_unstemmed | Immunological Significance of HMGB1 Post-Translational Modification and Redox Biology |
| title_short | Immunological Significance of HMGB1 Post-Translational Modification and Redox Biology |
| title_sort | immunological significance of hmgb1 post translational modification and redox biology |
| topic | high mobility group box1 (HMGB1) oxidation inflammation therapeutic target danger-associated molecular pattern (DAMP) |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01189/full |
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