Investigating and targeting a new mechanism for promoting cancer growth by increasing protein synthesis
Carmen Herrera (Researcher, Falnes Group)
Up-regulation of translation is a hallmark of cancer cells and essential for cancer growth. Therefore, targeting the core components of protein translation machinery and related signaling pathways represent a promise for cancer therapy. eEF1A is a key component of the elongation translational machinery that brings the aminoacylated tRNA to the translating ribosome. Methylation of eEF1A by the dual methyltransferase (MTase) METTL13 promotes protein synthesis and cancer growth. METTL13-MTase I methylates K55, while -MTase II methylates the N-terminus in eEF1A, but the relative importance of these two methylation events in cancer is unclear. We aim to understand the different roles of the two METTL13 MTase domains in promoting cancer growth to explore its potential as a clinical target. By using a high throughput in vitro MTase domain activity-based assay and the Epigenetic and Prestwick compound libraries, we have developed a drug-library screening for METTL13 inhibitors identification. We have identified several hits and further developed cell based- validation assays.