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

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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.

Original languageEnglish
Article number820
JournalBiomolecules
Volume10
Issue number6
DOIs
StatePublished - Jun 2020

Bibliographical note

Funding Information:
This work is supported by the Global Frontier (NRF-M3A6A4-2010-0029785 [S.K.], NRF-2013M3A6A4044991 [H.S.], and NRF-2015M3A6A4065724 [N.H.K]) National Research Foundation funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea.

Funding Information:
Funding: This work is supported by the Global Frontier (NRF-M3A6A4-2010-0029785 [S.K.], NRF-2013M3A6A4044991 [H.S.], and NRF-2015M3A6A4065724 [N.H.K]) National Research Foundation funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • AIMP2-DX2
  • Antibody
  • Diagnostic marker
  • Phage display
  • Splice variant

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