High mobility group box 1 protein (HMGB1) (HMGB1)

High mobility group box 1 protein (HMGB1) is a highly conserved, non-histone nuclear protein that functions as a DNA chaperone, stabilizing nucleosomes and regulating transcription (UniProt P09429). However, HMGB1 can be released into the extracellular environment during cell death (necrosis) or actively secreted by stressed immune cells, where it acts as a prototypical Damage-Associated Molecular Pattern (DAMP) (Andersson & Tracey, 2011). Once extracellular, HMGB1 binds to several receptors, most notably the Receptor for Advanced Glycation End-products (RAGE) and Toll-like receptors 2 and 4 (TLR2/4), triggering pro-inflammatory signaling pathways (Kang et al., 2014). This protein is a critical mediator in the pathogenesis of sepsis, rheumatoid arthritis, and various cancers, where it supports inflammation, angiogenesis, and metastasis. Therapeutic strategies targeting HMGB1 include the use of neutralizing antibodies, small molecule inhibitors like glycyrrhizin that bind directly to the protein, and agents that prevent its translocation from the nucleus to the cytoplasm.

Other names

HMG-1AmphoterinHMG1High mobility group protein B1

Direct binding and neutralization of extracellular HMGB1, inhibition of nucleocytoplasmic translocation and active secretion, and competitive inhibition of receptor binding (RAGE/TLR4).