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

Jin Woo Choi, Dae Gyu Kim, Al Eum Lee, Hye Rim Kim, Jin Young Lee, Nam Hoon Kwon, Young Kee Shin, Soon Kyung Hwang, Seung Hee Chang, Myung Haing Cho, Yoon La Choi, Jhingook Kim, Seung Hyun Oh, Bora Kim, Soo Youl Kim, Hyo Sung Jeon, Jae Yong Park, Hyunseok Peter Kang, Bum Joon Park, Jung Min HanSunghoon Kim

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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.

Original languageEnglish
Article numbere1001351
JournalPLoS Genetics
Volume7
Issue number3
DOIs
Publication statusPublished - 2011 Mar 1

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All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Choi, J. W., Kim, D. G., Lee, A. E., Kim, H. R., Lee, J. Y., Kwon, N. H., Shin, Y. K., Hwang, S. K., Chang, S. H., Cho, M. H., Choi, Y. L., Kim, J., Oh, S. H., Kim, B., Kim, S. Y., Jeon, H. S., Park, J. Y., Kang, H. P., Park, B. J., ... Kim, S. (2011). Cancer-associated splicing variant of tumor suppressor AIMP2/p38: Pathological implication in tumorigenesis. PLoS Genetics, 7(3), [e1001351]. https://doi.org/10.1371/journal.pgen.1001351