Description
HMGB1 is a nuclear protein that is released passively by necrotic cells, retained by apoptotic cells, and secreted actively by inflammatory cells.
HMGB1 is essential for life: HMGB1 knockout mice die shortly after birth. HMGB1 contains three conserved cysteine residues (C23, C45 and C106) and is a redox-sensitive. Chemotaxis-HMGB1 (the form with chemoattractant activity) is completely reduced; cytokine-HMGB1 contains a disulfide bond between C23 and C45; further oxidation to sulfonates abrogates both activities. In non-oxidizable chemokine-HMGB1 all cysteines are replaced with serines: these replacements preserve chemoattractant activity in vitro and in vivo, eliminate the cytokine-inducing activity and make the protein resistant to inactivation by ROS.