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An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody

 Dae Gyu Kim  ;  Thi Thu Ha Nguyen  ;  Nam Hoon Kwon  ;  Junsik Sung  ;  Semi Lim  ;  Eun-Joo Kang  ;  Jihye Lee  ;  Woo Young Seo  ;  Arum Kim  ;  Yoon Soo Chang  ;  Hyunbo Shim  ;  Sunghoon Kim 
 BIOMOLECULES, Vol.10(6) : 820, 2020-05 
Journal Title
Issue Date
AIMP2-DX2 ; antibody ; diagnostic marker ; phage display ; splice variant
AIMP2-DX2, an exon 2-deleted splice variant of AIMP2 (aminoacyl-tRNA synthetase-interacting multifunctional protein 2), is highly expressed in lung cancer and involved in tumor progression in vivo. Oncogenic function of AIMP2-DX2 and its correlation with poor prognosis of cancer patients have been well established; however, the application of this potentially important biomarker to cancer research and diagnosis has been hampered by a lack of antibodies specific for the splice variant, possibly due to the poor immunogenicity and/or stability of AIMP2-DX2. In this study a monoclonal antibody, H5, that specifically recognizes AIMP2-DX2 and its isoforms was generated via rabbit immunization and phage display techniques, using a short peptide corresponding to the exon 1/3 junction sequence as an antigen. Furthermore, based on mutagenesis, limited cleavage, and mass spectrometry studies, it is also suggested that the endogenous isoform of AIMP2-DX2 recognized by H5 is produced by proteolytic cleavage of 33 amino acids from N-terminus and is capable of inducing cell proliferation similarly to the uncleaved protein. H5 monoclonal antibody is applicable to enzyme-linked immunosorbent assay, immunoblot, immunofluorescence, and immunohistochemistry, and expected to be a valuable tool for detecting AIMP2-DX2 with high sensitivity and specificity for research and diagnostic purposes.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Chang, Yoon Soo(장윤수) ORCID logo https://orcid.org/0000-0003-3340-4223
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