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

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2020 Mar 3

PMID 32117966

Citations 5

Authors

Eunbyul Yeom

Dae-Woo Kwon

Jaemin Lee

Seok-Ho Kim

Ji-Hyeon Lee

Kyung-Jin Min

Kyu-Sun Lee

Kweon Yu

Affiliations

Soon will be listed here.

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. and the NRS inhibitor tirandamycin B (TirB) suppressed Yorkie-mediated tumor phenotypes in . Genetic analysis showed that interacted with Salvador, and 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.

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