Lysine-specific demethylase 4C (KDM4C) (KDM4C)

Lysine-specific demethylase 4C (KDM4C), also known as Jumonji domain-containing protein 2C (JMJD2C), is a member of the Jumonji-C (JmjC) domain-containing family of histone demethylases that plays a pivotal role in epigenetic regulation [1]. It specifically targets the tri- and di-methylated states of histone H3 lysine 9 (H3K9me3/2) and lysine 36 (H3K36me3/2), converting them to lower methylation states through an oxidative reaction requiring iron and alpha-ketoglutarate [1, 2]. By modulating these repressive and active chromatin marks, KDM4C regulates the expression of genes involved in the cell cycle, DNA replication, and pluripotency [3]. In oncology, KDM4C is frequently characterized as an epigenetic oncogene, with its gene (GASC1) often amplified or overexpressed in various malignancies, including breast, prostate, and esophageal cancers [4, 5]. Therapeutic strategies targeting KDM4C focus on small-molecule inhibitors that block its catalytic activity to restore normal chromatin states and inhibit tumor progression [5, 6]. Current research is directed toward improving the selectivity of these inhibitors to minimize off-target effects on other KDM4 family members and exploring their potential in combination with other chemotherapeutic agents [6]. Sources: [1] UniProt (O94953); [2] NCBI Gene (23081); [3] Cancer Res 2013;73(10):2936-42; [4] Nature 2006;442(7100):307-11; [5] Future Oncol 2018;14(26):2747-58; [6] Clin Epigenetics 2014;6(1):1-14.

Other names

Jumonji domain-containing protein 2CJMJD2CGASC1Gene amplified in squamous cell carcinoma 1JHDM3CLysine-specific demethylase 4C

Inhibition of the JmjC domain-mediated oxidative demethylation of tri- and di-methylated histone H3 lysine 9 (H3K9me3/2) and lysine 36 (H3K36me3/2).