Description: High-mobility group box-1 (HMGB1) protein was originally described as a nuclear non-histone DNA binding chromosomal protein. However, recent studies indicate that damaged, necrotic cells liberate HMGB1 into the extracellular milieu where it functions as a proinflammatory cytokine. Mouse HMGB1 is expressed as a 215 amino acid single chain polypeptide containing three domains: two tandem-linked positively charged DNA-binding domains (HMG box A, aa 9-79; and box B, aa 89-162), and a negatively charged 30 aa C-terminal acidic tail region. Residues 28 - 44 and 180 - 185 contain a nuclear localization signal (NLS). The cytokine activity of HMGB1 is contained in the B box, while the A box is associated with the helix-loop-helix domain of transcription factors. HMGB1 acts both as an inflammatory mediator that promotes monocyte migration and cytokine secretion, as well as a mediator of T cell-dendritic cell interaction. HMGB1 is secreted and acts to transduce cellular signals through its high affinity receptor, RAGE and possibly, TLR2 and TLR4.
