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Identification and structure of AIMP2-DX2 for therapeutic perspectives

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Regulation of cell fate and lung cell differentiation is associatedwith Aminoacyl-tRNA synthetases (ARS)-interacting multifunctionalprotein 2 (AIMP2), which acts as a non-enzymatic componentrequired for the multi-tRNA synthetase complex. In responseto DNA damage, a component of AIMP2 separates fromthe multi-tRNA synthetase complex, binds to p53, and preventsits degradation by MDM2, inducing apoptosis. Additionally,AIMP2 reduces proliferation in TGF- and Wnt pathways, whileenhancing apoptotic signaling induced by tumor necrosis factor-. Given the crucial role of these pathways in tumorigenesis,AIMP2 is expected to function as a broad-spectrum tumorsuppressor. The full-length AIMP2 transcript consists of fourexons, with a small section of the pre-mRNA undergoing alternativesplicing to produce a variant (AIMP2-DX2) lacking thesecond exon. AIMP2-DX2 binds to FBP, TRAF2, and p53 similarlyto AIMP2, but competes with AIMP2 for binding to thesetarget proteins, thereby impairing its tumor-suppressive activity. AIMP2-DX2 is specifically expressed in a diverse range of cancercells, including breast cancer, liver cancer, bone cancer,and stomach cancer. There is growing interest in AIMP2-DX2as a promising biomarker for prognosis and diagnosis, withAIMP2-DX2 inhibition attracting significant interest as a potentiallyeffective therapeutic approach for the treatment of lung,ovarian, prostate, and nasopharyngeal cancers.

Abstract

Regulation of cell fate and lung cell differentiation is associatedwith Aminoacyl-tRNA synthetases (ARS)-interacting multifunctionalprotein 2 (AIMP2), which acts as a non-enzymatic componentrequired for the multi-tRNA synthetase complex. In responseto DNA damage, a component of AIMP2 separates fromthe multi-tRNA synthetase complex, binds to p53, and preventsits degradation by MDM2, inducing apoptosis. Additionally,AIMP2 reduces proliferation in TGF- and Wnt pathways, whileenhancing apoptotic signaling induced by tumor necrosis factor-. Given the crucial role of these pathways in tumorigenesis,AIMP2 is expected to function as a broad-spectrum tumorsuppressor. The full-length AIMP2 transcript consists of fourexons, with a small section of the pre-mRNA undergoing alternativesplicing to produce a variant (AIMP2-DX2) lacking thesecond exon. AIMP2-DX2 binds to FBP, TRAF2, and p53 similarlyto AIMP2, but competes with AIMP2 for binding to thesetarget proteins, thereby impairing its tumor-suppressive activity. AIMP2-DX2 is specifically expressed in a diverse range of cancercells, including breast cancer, liver cancer, bone cancer,and stomach cancer. There is growing interest in AIMP2-DX2as a promising biomarker for prognosis and diagnosis, withAIMP2-DX2 inhibition attracting significant interest as a potentiallyeffective therapeutic approach for the treatment of lung,ovarian, prostate, and nasopharyngeal cancers.

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