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

Sunghoon Kim, 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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Keywords: AIMP2-DX2; antibody; diagnostic marker; phage display; splice variant.
Original languageEnglish
Pages (from-to)E820
JournalBiomolecules
Volume10
Issue number6
DOIs
Publication statusPublished - 2020 May 27

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