Lysine demethylase 8 (KDM8)

Lysine demethylase 8 (KDM8, also known as JMJD5) is a member of the Jumonji-C (JmjC) domain-containing family of histone demethylases, enzymes that catalyze the removal of methyl groups from histone H3 at lysine 36 (H3K36me2), modulating chromatin structure and gene expression. KDM8 plays a multifaceted role in cell cycle regulation, cell proliferation, and tumor metabolism, functioning as a transcriptional activator and coactivator for signaling and metabolic proteins (such as androgen receptor and PKM2). KDM8 overexpression is associated with oncogenesis, metabolic reprogramming (including the Warburg effect), and development of castration- or therapy-resistant cancer phenotypes. KDM8 is under active research as a therapeutic target in oncology, though pharmacological inhibition is at a preclinical or experimental stage and not yet clinically established.

Other names

JMJD5Jumonji domain-containing protein 5

Inhibition of enzymatic demethylase activity leads to altered chromatin states and gene expression, particularly repression of genes involved in cell cycle progression and glycolysis in cancer models. Combinatorial inhibition (e.g., EZH2 and KDM8) can re-sensitize tumor cells to hormonal therapies by destabilizing adaptive transcriptional and metabolic programs.