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Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11206-11. doi: 10.1073/pnas.0800297105. Epub 2008 Aug 11.

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

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  • 1Center for Medicinal Protein Network and Systems Biology, College of Pharmacy, and College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.

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.

PMID:
18695251
[PubMed - indexed for MEDLINE]
PMCID:
PMC2516205
Free PMC Article

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