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 Han & 1 others Sunghoon Kim

Research output: Contribution to journalArticle

41 Citations (Scopus)

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

Fingerprint

tumor
carcinogenesis
cancer
Carcinogenesis
neoplasms
lung neoplasms
Lung Neoplasms
Neoplasms
Amino Acyl-tRNA Synthetases
Competitive Binding
alternative splicing
apoptosis
Alternative Splicing
carcinogen
carcinogens
ligases
Carcinogens
DNA damage
DNA Damage
exons

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., ... 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
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. / Cancer-associated splicing variant of tumor suppressor AIMP2/p38 : Pathological implication in tumorigenesis. In: PLoS Genetics. 2011 ; Vol. 7, No. 3.
@article{5f23049b3cce4206856868057d1dffd6,
title = "Cancer-associated splicing variant of tumor suppressor AIMP2/p38: Pathological implication in tumorigenesis",
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.",
author = "Choi, {Jin Woo} and Kim, {Dae Gyu} and Lee, {Al Eum} and Kim, {Hye Rim} and Lee, {Jin Young} and Kwon, {Nam Hoon} and Shin, {Young Kee} and Hwang, {Soon Kyung} and Chang, {Seung Hee} and Cho, {Myung Haing} and Choi, {Yoon La} and Jhingook Kim and Oh, {Seung Hyun} and Bora Kim and Kim, {Soo Youl} and Jeon, {Hyo Sung} and Park, {Jae Yong} and Kang, {Hyunseok Peter} and Park, {Bum Joon} and Han, {Jung Min} and Sunghoon Kim",
year = "2011",
month = "3",
day = "1",
doi = "10.1371/journal.pgen.1001351",
language = "English",
volume = "7",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "3",

}

Choi, JW, Kim, DG, Lee, AE, Kim, HR, Lee, JY, Kwon, NH, Shin, YK, Hwang, SK, Chang, SH, Cho, MH, Choi, YL, Kim, J, Oh, SH, Kim, B, Kim, SY, Jeon, HS, Park, JY, Kang, HP, Park, BJ, Han, JM & Kim, S 2011, 'Cancer-associated splicing variant of tumor suppressor AIMP2/p38: Pathological implication in tumorigenesis', PLoS Genetics, vol. 7, no. 3, e1001351. https://doi.org/10.1371/journal.pgen.1001351

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

In: PLoS Genetics, Vol. 7, No. 3, e1001351, 01.03.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cancer-associated splicing variant of tumor suppressor AIMP2/p38

T2 - Pathological implication in tumorigenesis

AU - Choi, Jin Woo

AU - Kim, Dae Gyu

AU - Lee, Al Eum

AU - Kim, Hye Rim

AU - Lee, Jin Young

AU - Kwon, Nam Hoon

AU - Shin, Young Kee

AU - Hwang, Soon Kyung

AU - Chang, Seung Hee

AU - Cho, Myung Haing

AU - Choi, Yoon La

AU - Kim, Jhingook

AU - Oh, Seung Hyun

AU - Kim, Bora

AU - Kim, Soo Youl

AU - Jeon, Hyo Sung

AU - Park, Jae Yong

AU - Kang, Hyunseok Peter

AU - Park, Bum Joon

AU - Han, Jung Min

AU - Kim, Sunghoon

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79953766254&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953766254&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1001351

DO - 10.1371/journal.pgen.1001351

M3 - Article

VL - 7

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 3

M1 - e1001351

ER -