SMYD5 methylation of rpL40 links ribosomal output to gastric cancer.

ABSTRACT: Dysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis^1,2. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 (rpL40) at lysine 22 (rpL40K22me3) by the lysine methyltransferase SMYD5 regulates mRNA translation output to promote malignant progression of gastric adenocarcinoma (GAC) with lethal peritoneal ascites. A biochemical-proteomics strategy identifies the monoubiquitin fusion protein partner rpL40 (ref. ³) as the principal physiological substrate of SMYD5 across diverse samples. Inhibiting the SMYD5-rpL40K22me3 axis in GAC cell lines reprogrammes prot

SUBMITTER: Park J 

PROVIDER: S-EPMC11625416 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature