AUTHOR=Yeom Eunbyul , Kwon Dae-Woo , Lee Jaemin , Kim Seok-Ho , Lee Ji-Hyeon , Min Kyung-Jin , Lee Kyu-Sun , Yu Kweon 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00032

DOI=10.3389/fcell.2020.00032

ISSN=2296-634X

ABSTRACT=<p>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. <italic>NRS-RNAi</italic> and the NRS inhibitor tirandamycin B (TirB) suppressed Yorkie-mediated tumor phenotypes in <italic>Drosophila</italic>. Genetic analysis showed that <italic>NRS</italic> interacted with Salvador, and <italic>NRS</italic> 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 inhibited NRS-Salvador binding. YAP target genes were upregulated in a mammalian cancer cell line with high expression of NRS, whereas TirB treatment suppressed cancer cell proliferation. These results indicate that NRS regulates tumor growth by interacting with Salvador in the Hippo signaling pathway.</p>