Lysine-specific demethylase 6B (KDM6B) (KDM6B)

Histone demethylase JMJD3, officially known as Lysine-specific demethylase 6B (KDM6B), is a JmjC domain-containing enzyme that plays a pivotal role in epigenetic regulation by specifically demethylating the repressive H3K27me3 and H3K27me2 marks on histone H3 [UniProt, 2024]. By removing these methyl groups, JMJD3 facilitates the transition of chromatin from a repressed to an active state, thereby promoting the transcription of genes involved in cell fate determination, inflammatory responses, and cellular senescence [NIH, 2021]. It is highly inducible by various stimuli, including inflammatory cytokines and stress signals, and is a critical mediator of macrophage polarization and T-cell differentiation [PubMed, 2014]. In oncology, JMJD3 exhibits a complex, context-dependent dual role; it acts as an oncogene in malignancies such as T-cell acute lymphoblastic leukemia and glioblastoma by activating pro-proliferative pathways, yet it can function as a tumor suppressor in other contexts, such as pancreatic cancer, by inducing senescence [ResearchGate, 2021]. Pharmacological targeting of JMJD3 has primarily utilized small-molecule inhibitors like GSK-J4, which serves as a potent tool compound in preclinical research to suppress tumor growth and alleviate inflammatory conditions [PubMed, 2023]. However, no JMJD3-specific inhibitors have successfully transitioned to clinical trials to date, largely due to challenges regarding isoform selectivity and the potential for adverse effects stemming from the enzyme's essential roles in normal development and tissue homeostasis [NIH, 2023].

Other names

JMJD3Jumonji domain-containing protein 3KDM6BLysine-specific demethylase 6B

Inhibition of the JmjC catalytic domain to prevent the demethylation of H3K27me3/me2, thereby maintaining gene repression.