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

Cited 75 time in Web of Science Cited 77 time in Scopus
Authors
Han, Jung Min; Park, Bum-Joon; Park, Sang Gyu; Oh, Young Sun; Choi, So Jung; Lee, Sang Won; Hwang, Soon-Kyung; Chang, Seung-Hee; Cho, Myung-Haing; Kim, Sunghoon
Issue Date
2008-08
Citation
Proceedings of the National Academy of Sciences of the United States of America, Vol.105 No.32, pp.11206-11211
Keywords
aminoacyl-tRNA synthetaseJNKapoptosisDNA damagemdm2
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.
ISSN
0027-8424
URI
https://hdl.handle.net/10371/172506
DOI
https://doi.org/10.1073/pnas.0800297105
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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