HMGB1: AN OVERVIEW
HMGB1, previously named HMG1 or amphoterin, belongs to the High Mobility Group (HMG) proteins, a category of nuclear DNA-binding proteins that are widely expressed in most mammalian cells.
HMGs were named according to their electrophoretic mobility in polyacrylamide gels. HMGB1 is especially abundant in mammalian cells nuclei (more than one million molecules per cell). Since its discovery HMGB1 has been mostly analyzed for its various functions in the nucleus. However, recent studies uncovered a quite unexpected albeit presumably essential activity for HMGB1. In addition to its nuclear activity, HMGB1 was indeed demonstrated to act outside of the cells where it behaves as a potent intercellular mediator. Extracellular forms of HMGB1 may provide either from an active secretion in immuno-competent cells such as activated macrophages or natural killer cells, or from a passive release in cells whose plasma membrane has been damaged, such as necrotic cells.Under this form, HMGB1 may coordinate various cell responses linking septic or aseptic stress signals to innate immunity and tissue repair. Due to this property, HMGB1 is now considered as the main prototype of the “damage-associated pattern molecules” (DAMPs) called “alarmins”.
The B box also contains the cytokine activity of HMGB1. The first 20 amino acids of the B box induce TNF release from macrophages, whereas residues 106-123 are sufficient to induce IL6 secretion from dendritic cells [31, 90, 91]. The domain involved in the binding of HMGB1 to RAGE is located between amino acid residues 150 and 183 [9, 35].