The T1150A cancer mutant of the protein lysine dimethyltransferase NSD2 can introduce H3K36 trimethylation.

ABSTRACT: Protein lysine methyltransferases (PKMTs) play essential roles in gene expression regulation and cancer development. Somatic mutations in PKMTs are frequently observed in cancer cells. In biochemical experiments, we show here that the NSD1 mutations Y1971C, R2017Q, and R2017L observed mostly in solid cancers are catalytically inactive suggesting that NSD1 acts as a tumor suppressor gene in these tumors. In contrast, the frequently observed T1150A in NSD2 and its T2029A counterpart in NSD1, both observed in leukemia, are hyperactive and introduce up to three methyl groups in H3K36 in biochemical and cellular assays, while wildtype NSD2 and NSD1 only introduce up to two methyl groups. In Molecular Dynamics simulations, we determined key mechanistic and structural features controlling the pro

SUBMITTER: Khella MS 

PROVIDER: S-EPMC10244704 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature