Lysine-specific demethylase 3B (KDM3B)

Lysine-specific demethylase 3B (KDM3B) is an epigenetic enzyme of the Jumonji C (JmjC) domain-containing family that catalyzes the demethylation of mono- and di-methylated lysine 9 on histone H3 (H3K9me1 and H3K9me2), generally promoting activation of gene transcription[1][3][4][5][8]. KDM3B is involved in regulating diverse biological processes, including cell proliferation, differentiation, metabolism, autophagy, and female reproduction[1][3][8]. It plays critical roles both in normal development and disease, with evidence supporting tumor suppressor activities (notably in myelodysplasia and breast cancer), although it may also facilitate oncogenesis in certain leukemia subtypes, reflecting context-dependent functions[1][2][5][6]. KDM3B is considered a therapeutic target for cancers, especially those with deletions of the 5q locus, and is currently being explored for small molecule modulation[2]. Disruption of KDM3B function impacts key physiological pathways such as IGF-1 signaling, chromatin state regulation, and tissue regeneration[1][3][4].

Other names

JMJD1BJHDM2B5qNCAC5orf7KIAA1082NET22DIJOSJumonji domain-containing protein 1BJmjC domain-containing histone demethylation protein 2B[histone H3]-dimethyl-L-lysine(9) demethylase 3B

Small molecule agonists (e.g., KA-7) enhance KDM3B enzymatic activity, leading to increased H3K9 demethylation and transcriptional activation. Synergistic cytotoxicity with Lenalidomide, possibly through enhanced epigenetic reprogramming in leukemia with 5q deletion.