High-mobility group box 1 (HMGB1)

High-mobility group box 1 (HMGB1) is a highly conserved nuclear protein that normally functions as a DNA chaperone, facilitating transcription, DNA repair, and nucleosome stability (UniProt P09429). However, when released into the extracellular environment by necrotic cells or actively secreted by stressed immune cells, it acts as a prototypical damage-associated molecular pattern (DAMP) (PubMed: 15851690). Extracellular HMGB1 triggers potent pro-inflammatory responses by binding to several receptors, most notably the Receptor for Advanced Glycation End-products (RAGE) and Toll-like receptor 4 (TLR4) (PubMed: 11387483). The HMGB1-RAGE interaction, specifically mediated by the B-box domain of HMGB1, is a critical driver of chronic inflammation, angiogenesis, and metastasis in various cancers (PubMed: 23233724). Therapeutic strategies targeting this axis include small molecule inhibitors like glycyrrhizin, which binds directly to HMGB1, and monoclonal antibodies or RAGE antagonists like FPS-ZM1 designed to disrupt the HMGB1-RAGE binding interface (PubMed: 17210728, 22586015).

Other names

AmphoterinHMG-1High mobility group protein 1HMG1HMG-B1

Inhibition of HMGB1 release from the nucleus, neutralization of extracellular HMGB1 via monoclonal antibodies, or competitive inhibition of the HMGB1-RAGE binding interface to prevent pro-inflammatory signaling.