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Antioxid Redox Signal. 2016 Apr 20;24(12):620-34. doi: 10.1089/ars.2015.6409. Epub 2016 Feb 5.

Regulation of Posttranslational Modifications of HMGB1 During Immune Responses.

Author information

1
1 Department of Hematology, The 3rd Xiangya Hospital, Central South University , Changsha, China .
2
2 State Key Laboratory of Medical Genetics, School of Biological Science and Technology, Central South University , Changsha, China .
3
3 Department of Physiology, Xiangya School of Medicine, Central South University , Changsha, China .
4
4 Department of Molecular and Clinical Pharmacology, Medical Research Council Centre for Drug Safety Science, University of Liverpool , Liverpool, United Kingdom .
5
5 Hunan Province Key Laboratory of Sepsis and Translational Medicine, Xiangya School of Medicine, Central South University , Changsha, China .
6
6 Department of Pathophysiology, Xiangya School of Medicine, Central South University , Changsha, China .
7
7 Department of Emergency Medicine, North Shore University Hospital , Manhasset, New York.
8
8 Department of Women's and Children's Health, Karolinska Institutet , Stockholm, Sweden .
9
9 Department of Surgery, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
10
10 Center of Biomedical Science, Feinstein Institute for Medical Research , Manhasset, New York.

Abstract

SIGNIFICANCE:

High-mobility group protein 1 (HMGB1) is an evolutionarily conserved and multifunctional protein. The biological function of HMGB1 depends on its cellular locations, binding partners, and redox states. Extracellular HMGB1 is a mediator of inflammation during infection or tissue injury. Immune cells actively release HMGB1 in response to infection, which in turn orchestrates both innate and adaptive immune responses.

RECENT ADVANCES:

Hyperacetylation of HMGB1 within its nuclear localization sequences mobilizes HMGB1 from the nucleus to the cytoplasm and subsequently promotes HMGB1 release. The redox states of the cysteines in positions 23, 45, and 106 determine the biological activity of the extracellular HMGB1.

CRITICAL ISSUES:

The full picture and the detailed molecular mechanisms of how cells regulate the posttranslational modifications and the redox status of HMGB1 during immune responses or under stress not only unravel the molecular mechanisms by which cells regulate the release and the biological function of HMGB1 but may also provide novel therapeutic targets to treat inflammatory diseases.

FUTURE DIRECTIONS:

It is important to identify the signaling pathways that regulate the posttranslational modifications and the redox status of HMGB1 and find their roles in host immune responses and pathogenesis of diseases.

PMID:
26715031
PMCID:
PMC5349223
DOI:
10.1089/ars.2015.6409
[Indexed for MEDLINE]
Free PMC Article

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