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Cancer-associated splicing variant of tumor suppressor AIMP2/p38: Pathological implication in tumorigenesis

Cited 56 time in Web of Science Cited 57 time in Scopus
Authors
Choi, Jin Woo; Kim, Dae Gyu; Lee, Al-Eum; Kim, Hye Rim; Lee, Jin Young; Kwon, Nam Hoon; Shin, Young Kee; Hwang, Soon-Kyung; Chang, Seung-Hee; Cho, Myung-Haing; Choi, Yoon-La; Kim, Jhingook; Oh, Seung Hyun; Kim, Bora; Kim, Soo-Youl; Jeon, Hyo-Sung; Park, Jae Yong; Kang, Hyunseok Peter; Park, Bum Joon; Han, Jung Min; Kim, Sunghoon
Issue Date
2011-03
Publisher
Public Library of Science
Citation
PLoS Genetics, Vol.7 No.3, p. e1001351
Abstract
Although ARS-interacting multifunctional protein 2 (AIMP2, also named as MSC p38) was first found as a component for a macromolecular tRNA synthetase complex, it was recently discovered to dissociate from the complex and work as a potent tumor suppressor. Upon DNA damage, AIMP2 promotes apoptosis through the protective interaction with p53. However, it was not demonstrated whether AIMP2 was indeed pathologically linked to human cancer. In this work, we found that a splicing variant of AIMP2 lacking exon 2 (AIMP2-DX2) is highly expressed by alternative splicing in human lung cancer cells and patient's tissues. AIMP2-DX2 compromised pro-apoptotic activity of normal AIMP2 through the competitive binding to p53. The cells with higher level of AIMP2-DX2 showed higher propensity to form anchorage-independent colonies and increased resistance to cell death. Mice constitutively expressing this variant showed increased susceptibility to carcinogen-induced lung tumorigenesis. The expression ratio of AIMP2-DX2 to normal AIMP2 was increased according to lung cancer stage and showed a positive correlation with the survival of patients. Thus, this work identified an oncogenic splicing variant of a tumor suppressor, AIMP2/p38, and suggests its potential for anti-cancer target.
ISSN
1553-7390
Language
English
URI
https://hdl.handle.net/10371/78717
DOI
https://doi.org/10.1371/journal.pgen.1001351
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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