Cancer-Associated Splicing Variant of Tumor Suppressor AIMP2/p38: Pathological Implication in Tumorigenesis

• DOI: 10.1371/journal.pgen.1001351
• Publication Date: 2011-03-31T21:14:20Z
• Authors: 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; Sunghoon Kim
• Keywords: Male; 0301 basic medicine; Lung Neoplasms; Adenocarcinoma of Lung; Apoptosis; QH426-470; Adenocarcinoma; Amino Acyl-tRNA Synthetases; Mice; 03 medical and health sciences; Cell Line, Tumor; Genetics; Animals; Humans; Aged; Neoplasm Staging; Exons; Middle Aged; Survival Analysis; 3. Good health; Gene Expression Regulation, Neoplastic; Alternative Splicing; Cell Transformation, Neoplastic; Female; Tumor Suppressor Protein p53; Research Article

Although ARS-interacting multifunctional protein 2 (AIMP2, also named as MSC p38) was first found a component for macromolecular tRNA synthetase complex, it recently discovered to dissociate from the complex and work potent tumor suppressor. Upon DNA damage, AIMP2 promotes apoptosis through protective interaction with p53. However, not demonstrated whether indeed pathologically linked human cancer. In this work, we that splicing variant of lacking exon (AIMP2-DX2) is highly expressed by alternative in lung cancer cells patient's tissues. AIMP2-DX2 compromised pro-apoptotic activity normal competitive binding The higher level showed propensity form anchorage-independent colonies increased resistance cell death. Mice constitutively expressing susceptibility carcinogen-induced tumorigenesis. expression ratio according stage positive correlation survival patients. Thus, identified an oncogenic suppressor, AIMP2/p38, suggests its potential anti-cancer target.