Lysine-specific demethylase 4A (KDM4A) (KDM4A)

Lysine-specific demethylase 4A (KDM4A), also known as JMJD2A, is a member of the Jumonji C (JmjC) domain-containing family of histone demethylases that plays a critical role in epigenetic regulation (UniProt: O75164). It specifically catalyzes the demethylation of tri-methylated and di-methylated lysine 9 and lysine 36 on histone H3 (H3K9me2/3 and H3K36me2/3), which are marks typically associated with transcriptional repression and activation, respectively (PubMed: 16603238). KDM4A is frequently overexpressed in various malignancies, including breast, prostate, and colorectal cancers, where it promotes cell cycle progression and suppresses apoptosis (PubMed: 22491021). Beyond its role in oncology, KDM4A has been identified as a key regulator of inflammatory cytokine signaling, particularly through its interaction with the NF-kappaB pathway and its ability to modulate the chromatin environment at the promoters of genes like IL-6 and TNF-alpha (PubMed: 31434684). Therapeutic strategies targeting KDM4A involve small-molecule inhibitors like ML324 and QC6352, which are designed to block its catalytic activity, thereby restoring repressive histone marks and dampening aberrant gene expression in cancer and inflammatory diseases (PubChem: CID 56924025). The input name "KDM4A and inflammatory cytokine signaling pathway components" is considered incorrect as a single target designation because it combines a specific enzyme with a broad biological pathway.

Other names

Jumonji domain-containing protein 2AJMJD2AJHDM3AKDM4A

Inhibition of the JmjC domain-mediated demethylation of H3K9me2/3 and H3K36me2/3, which modulates the expression of genes involved in cell proliferation and the inflammatory response.