Histone-lysine N-methyltransferase NSD3 (NSD3)

Histone-lysine N-methyltransferase NSD3 (NSD3) is an epigenetic enzyme in the nuclear receptor-binding SET domain family, catalyzing mono- and dimethylation of histone H3 at lysine 36 (H3K36). This mark is associated with active transcription, and NSD3 is a key regulator of chromatin structure and gene expression. NSD3 is frequently overexpressed, amplified, or mutated in numerous cancers, where it drives oncogenic signaling, boosts transcription of cancer-related genes (such as MYC, NOTCH3, Adam12, Prkaa2), and activates cell growth and proliferation pathways, including mTOR signaling. Silencing or genetic knockout of NSD3 suppresses cancer cell proliferation, migration, invasion, and induces apoptosis and cell cycle arrest. NSD3, also known as WHSC1L1, is a potential therapeutic target for oncology, although no clinically approved drugs directly targeting NSD3 are yet available[1][2][3].

Other names

Nuclear receptor binding SET domain protein 3WHSC1L1KMT3FKMT3GNuclear SET domain-containing protein 3Protein whistleWHISTLEWolf-Hirschhorn syndrome candidate 1-like 1DC28FLJ20353WHSC1-like 1WHSC1-like protein 1NSD3, isoform 9 with methyltransferase activity to lysine

(For anticancer NSD3 inhibitors in preclinical development): Inhibition of H3K36 methylation, which leads to reduced transcription of oncogenes, impaired cell proliferation, cell cycle arrest, and apoptosis induction in cancer cells[1][2].