High mobility group protein B3 (HMGB3)

High mobility group protein B3 (HMGB3) is a non-histone chromatin-binding protein characterized by its high electrophoretic mobility and architectural role in chromatin structure. HMGB3 contains two DNA-binding domains (HMG-box A and B) and a C-terminal acidic tail. It is involved in the regulation of DNA repair, replication, recombination, and transcription, and plays an important role in stem cell maintenance and differentiation. HMGB3 is frequently overexpressed in many cancers, where its increased levels promote proliferation, migration, and invasion. It modulates key oncogenic pathways such as WNT/β‐catenin and MAPK, enhancing tumor aggressiveness and resistance to therapy. HMGB3 regulates gene expression by binding to and shaping non-canonical DNA structures and is implicated in the innate immune response by functioning as a promiscuous DNA/RNA sensor. Knockdown of HMGB3 in cancer cells leads to increased apoptosis and reduced colony formation, supporting its candidacy as a therapeutic target[1][2][3][4][5][6].

Other names

HMG2AHMG4HMG-2aHMG-4MGC90319High mobility group protein 2aHigh mobility group protein 4Non-histone chromosomal proteinHigh-mobility group (nonhistone chromosomal) protein 4

RNA interference/shRNA knockdown leads to decreased viability/colony formation and increased apoptosis in cancer cells, primarily through intrinsic apoptosis activation (increased Bax/Bcl-2 ratio and caspase-9 activation). Small molecule inhibition, if developed, would likely target HMGB3’s DNA-binding or protein-interaction domains to block its effect on chromatin structure or gene regulation.