Title:Dichotomous Life of DNA Binding High Mobility Group Box1 Protein in Human Health and Disease
Volume: 17
Issue: 8
Author(s): Neelam Lohani and Moganty R. Rajeswari
Affiliation:
Keywords:
HMGB1, Cytokine, Chromatin, Cancer, Inflammation, Intracellular, Extracellular, DAMP (Damage associated
molecular pattern molecule).
Abstract: The High mobility group box 1 (HMGB1) protein is an extremely versatile, highly conserved
nuclear protein, with its unique intracellular and extracellular functions mediated by its relatively
simple domain structure. Within the nucleus, HMGB1 binds to DNA minor groove in a nonspecific
manner and causes bends in the double helix thus helps in recruiting a number of DNA binding
protein and transcription factors, to facilitate transcription of various genes. HMGB1 also helps in
DNA repair, chromatin remodeling, V (D) J recombination, and assembly of nucleosome on the chromatin.
On contrary, under pathological conditions HMGB1 displays inflammatory response by interaction
with specific cell surface receptors like RAGE, TLR-4, TLR9, and TLR2 and activates NF-kB
downstream signaling pathways. The upregulation of HMGB1 is directly associated with the pathogenesis of cancer, sepsis,
ischemia, hemorrhagic shock, anorexia, rheumatic disease, periodontal disease etc. Therefore, HMGB1 has been considered
as a promising target in the treatment of various human diseases. The interest in HMGB1 is evident and reflected
in the exponential increase in the recent publications, and therefore there is a need for an update on the understanding of
the role of HMGB1 in pathogenesis and its potential application of HMGB1 as a therapeutic target in a number of human
diseases.
