Asparaginyl-tRNA Synthetase, a Novel Component of Hippo Signaling, Binds to Salvador and Enhances Yorkie-Mediated Tumorigenesis.

ABSTRACT: Aminoacyl-tRNA synthetases (ARSs), which are essential for protein translation, were recently shown to have non-translational functions in various pathological conditions including cancer. However, the molecular mechanism underlying the role of ARSs in cancer remains unknown. Here, we demonstrate that asparaginyl-tRNA synthetase (NRS) regulates Yorkie-mediated tumorigenesis by binding to the Hippo pathway component Salvador. NRS-RNAi and the NRS inhibitor tirandamycin B (TirB) suppressed Yorkie-mediated tumor phenotypes in Drosophila. Genetic analysis showed that NRS interacted with Salvador, and NRS activated Hippo target genes by regulating Yorkie phosphorylation. Biochemical analyses showed that NRS blocked Salvador-Hippo binding by interacting directly with Salvador, and TirB treatment

SUBMITTER: Yeom E 

PROVIDER: S-EPMC7014954 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature