Lysine-specific demethylase 5B (KDM5B)

Lysine-specific demethylase 5B (KDM5B) is a multi-domain enzyme encoded by the KDM5B gene in humans. As a member of the Jumonji C domain-containing histone demethylase family, its principal molecular function is removal of methyl groups from lysine 4 on histone H3 (specifically H3K4me3/me2), thereby repressing gene transcription in target genes involved in cell cycle, development, genome stability, and stem cell maintenance. KDM5B plays a key role in embryonic development, tissue differentiation, and self-renewal of stem cells. Its aberrant overexpression is implicated in the initiation, invasion, and metastasis of a variety of cancers, and it has become a promising therapeutic target and biomarker for cancer prognosis. Knockout and genetic studies show both crucial developmental and disease-related functions, as well as risks associated with its inhibition. KDM5B’s complex domain architecture allows interactions with protein partners (e.g., FOXG1B, PAX9) and DNA, contributing to its context-dependent regulatory roles in chromatin modification and transcription. Experimental inhibitors of KDM5B are being developed as potential cancer therapeutics, though clinical safety remains to be fully established.

Other names

JARID1BPLU-1PLU1RBP2-H1PPP1R9CT31PUT1MRT65RBBP2H1A

Drugs (small molecule inhibitors) target the catalytic JmjC domain, inhibiting H3K4 demethylase activity and thereby affecting gene repression and the transcriptional program of cancer cells. Potential mechanism: restoration of tumor suppressor gene expression and induction of cancer cell differentiation or cell cycle arrest.