High mobility group protein B1 (HMGB1) (HMGB1)

High mobility group protein B1 (HMGB1) is a highly conserved, ubiquitous non-histone nuclear protein that functions as a structural component of chromatin, facilitating DNA bending and regulating gene expression [5, 11]. In its intracellular role, it is essential for processes such as transcription, replication, and DNA repair [1, 5]. However, HMGB1 is also a prototypical "alarmin" or Damage-Associated Molecular Pattern (DAMP); it is released into the extracellular space either passively by necrotic cells or actively by stressed immune cells [4, 10]. Once extracellular, HMGB1 signals through the Receptor for Advanced Glycation End-products (RAGE) and Toll-Like Receptor 4 (TLR4) to initiate and amplify robust pro-inflammatory immune responses [3, 18]. This dual nature makes HMGB1 a critical mediator in diverse pathologies, including sepsis, autoimmune disorders like rheumatoid arthritis, and various cancers where it contributes to tumor progression and metastasis [5, 13, 20]. Therapeutic interventions focus on blocking HMGB1 secretion, neutralizing the protein with antibodies, or antagonizing its receptor interactions, although maintaining its beneficial nuclear functions remains a key therapeutic challenge [6, 14].

Other names

High mobility group box 1AmphoterinHMG1High-mobility group protein 1SBP-1

Drugs targeting HMGB1 typically function by inhibiting its translocation from the nucleus and subsequent active secretion from immune cells, directly neutralizing extracellular HMGB1 to prevent receptor binding, or acting as competitive antagonists at its primary receptors, such as RAGE and TLR4.