AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53

Min Han Jung, Bum Joon Park, Gyu Park Sang, Sun Oh Young, Jung Choi So, Won Lee Sang, Soon Kyung Hwang, Seung Hee Chang, Myung Haing Cho, Sunghoon Kim

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63 Citations (Scopus)

Abstract

AIMP2/p38 is a scaffolding protein required for the assembly of the macromolecular tRNA synthetase complex. Here, we describe a previously unknown function for AIMP2 as a positive regulator of p53 in response to genotoxic stresses. Depletion of AIMP2 increased resistance to DNA damage-induced apoptosis, and introduction of AIMP2 into AIMP2-deficient cells restored the susceptibility to apoptosis. Upon DNA damage, AIMP2 was phosphorylated, dissociated from the multi-tRNA synthetase complex, and translocated into the nuclei of cells. AIMP2 directly interacts with p53, thereby preventing MDM2-mediated ubiquitination and degradation of p53. Mutations in AIMP2, affecting its interaction with p53, hampered its ability to activate p53. Nutlin-3 recovered the level of p53 and the susceptibility to UV-induced cell death in AIMP2-deficient cells. This work demonstrates that AIMP2, a component of the translational machinery, functions as proapoptotic factor via p53 in response to DNA damage.

Original languageEnglish
Pages (from-to)11206-11211
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number32
DOIs
Publication statusPublished - 2008 Aug 12

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