Lysine-specific demethylase 2B (KDM2B)

Lysine-specific demethylase 2B (KDM2B) is a Fe(II)- and alpha-ketoglutarate-dependent histone demethylase characterized by a JmjC domain and additional DNA and protein interaction domains (CXXC zinc finger, PHD, F-box, leucine-rich repeats)[1][5]. This enzyme removes methyl groups from histone H3 lysine residues (H3K36me2, H3K4me3, H3K79me2/3), repressing gene transcription and influencing chromatin architecture[1][3][4][5]. KDM2B controls cell cycle progression, cell proliferation, senescence, stem cell maintenance, and differentiation. It is a core component of polycomb repressive complex 1 (PRC1), mediating gene silencing, and is overexpressed in several cancers, correlating with malignancy and metastasis[1][5]. KDM2B also regulates the timely dissociation of PCNA from chromatin during DNA synthesis, thus facilitating normal DNA replication and cell division[4]. Its role as a chromatin modulator makes it a proposed therapeutic target in cancer and other epigenetic diseases, but no selective and clinically approved KDM2B inhibitors are currently available.

Other names

CXXC2FBL10FBXL10JHDM1BNDY1PCCX2JEMMA proteinCXXC-type zinc finger protein 2F-box and leucine-rich repeat protein 10

Inhibitors would act by blocking the demethylase activity (JmjC domain), resulting in increased histone methylation marks and transcriptional activation of otherwise repressed genes. Potential modulation of DNA replication and cell cycle progression through altered interactions with chromatin and replication machinery.