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.
authors.affiliation: Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Choi
authors.forename: Dae Gyu
authors.initials: DG
authors.lastname: Kim
authors.forename: Al-Eum
authors.initials: AE
authors.lastname: Lee
authors.forename: Hye Rim
authors.initials: HR
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Kwon
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shin
authors.forename: Soon-Kyung
authors.initials: SK
authors.lastname: Hwang
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.forename: Jhingook
authors.initials: J
authors.lastname: Kim
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Oh
authors.forename: Bora
authors.initials: B
authors.lastname: Kim
authors.forename: Soo-Youl
authors.initials: SY
authors.lastname: Kim
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Hyunseok Peter
authors.initials: HP
authors.lastname: Kang
authors.forename: Bum Joon
authors.initials: BJ
authors.lastname: Park
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Han
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D017398:Alternative Splicing; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53; C474321:aminoacyl-tRNA synthetase-associated protein p38; D000604:Amino Acyl-tRNA Synthetases