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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Identification and structure of AIMP2-DX2 for therapeutic perspectives

  • Hyeon Jin Kim (Institute of Systems Biology, Pusan National University) ;
  • Mi Suk Jeong (Institute of Systems Biology, Pusan National University) ;
  • Se Bok Jang (Institute of Systems Biology, Pusan National University)
  • Received : 2024.04.10
  • Accepted : 2024.05.07
  • Published : 2024.07.31
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Abstract

Regulation of cell fate and lung cell differentiation is associated with Aminoacyl-tRNA synthetases (ARS)-interacting multifunctional protein 2 (AIMP2), which acts as a non-enzymatic component required for the multi-tRNA synthetase complex. In response to DNA damage, a component of AIMP2 separates from the multi-tRNA synthetase complex, binds to p53, and prevents its degradation by MDM2, inducing apoptosis. Additionally, AIMP2 reduces proliferation in TGF-β and Wnt pathways, while enhancing apoptotic signaling induced by tumor necrosis factor-α. Given the crucial role of these pathways in tumorigenesis, AIMP2 is expected to function as a broad-spectrum tumor suppressor. The full-length AIMP2 transcript consists of four exons, with a small section of the pre-mRNA undergoing alternative splicing to produce a variant (AIMP2-DX2) lacking the second exon. AIMP2-DX2 binds to FBP, TRAF2, and p53 similarly to AIMP2, but competes with AIMP2 for binding to these target proteins, thereby impairing its tumor-suppressive activity. AIMP2-DX2 is specifically expressed in a diverse range of cancer cells, including breast cancer, liver cancer, bone cancer, and stomach cancer. There is growing interest in AIMP2-DX2 as a promising biomarker for prognosis and diagnosis, with AIMP2-DX2 inhibition attracting significant interest as a potentially effective therapeutic approach for the treatment of lung, ovarian, prostate, and nasopharyngeal cancers.

Keywords

Acknowledgement

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Education, Science and Technology (Grant no. 2016R1D1A1B02011142) to M.S.J. and (Grant no. 2018R1D1A1B07043701) to S.B.J. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant no. RS-2023-00273615) to H.J.K. This research was supported by Learning & Academic research institution for Master's·PhD students, and Postdocs (LAMP) Program of the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education (No. RS-2023-00301938).

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