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Yeom, E., Kwon, D.W., Lee, J., Kim, S.H., Lee, J.H., Min, K.J., Lee, K.S., Yu, K. (2020). Asparaginyl-tRNA Synthetase, a Novel Component of Hippo Signaling, Binds to Salvador and Enhances Yorkie-Mediated Tumorigenesis.  Front. Cell Dev. Biol. 8(): 32.
FlyBase ID
FBrf0244980
Publication Type
Research paper
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 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.

PubMed ID
PubMed Central ID
PMC7014954 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Front. Cell Dev. Biol.
    Title
    Frontiers in cell and developmental biology
    ISBN/ISSN
    2296-634X
    Data From Reference