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Location is the key to function: HMGB1 in sepsis and trauma-induced inflammation

2019/04/04 by Meihong Deng, Melanie J Scott, Melanie J. Scott +3
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Advanced Glycation End Products research #Immune Response and Inflammation #S100 Proteins and Annexins

paper · doi:10.1002/jlb.3mir1218-497r

openalex publication_date 2019/04/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29

Abstract

High mobility group box 1 (HMGB1) is a multifunctional nuclear protein, probably known best as a prototypical alarmin or damage-associated molecular pattern (DAMP) molecule when released from cells. However, HMGB1 has multiple functions that depend on its location in the nucleus, in the cytosol, or extracellularly after either active release from cells, or passive release upon lytic cell death. Movement of HMGB1 between cellular compartments is a dynamic process induced by a variety of cell stresses and disease processes, including sepsis, trauma, and hemorrhagic shock. Location of HMGB1 is intricately linked with its function and is regulated by a series of posttranslational modifications. HMGB1 function is also regulated by the redox status of critical cysteine residues within the protein, and is cell-type dependent. This review highlights some of the mechanisms that contribute to location and functions of HMGB1, and focuses on some recent insights on important intracellular effects of HMGB1 during sepsis and trauma.

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