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

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 w...

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Autores principales: Kim, Dae Gyu, Nguyen, Thi Thu Ha, Kwon, Nam Hoon, Sung, Junsik, Lim, Semi, Kang, Eun-Joo, Lee, Jihye, Seo, Woo Young, Kim, Arum, Chang, Yoon Soo, Shim, Hyunbo, Kim, Sunghoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356629/
https://www.ncbi.nlm.nih.gov/pubmed/32471182
http://dx.doi.org/10.3390/biom10060820
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author Kim, Dae Gyu
Nguyen, Thi Thu Ha
Kwon, Nam Hoon
Sung, Junsik
Lim, Semi
Kang, Eun-Joo
Lee, Jihye
Seo, Woo Young
Kim, Arum
Chang, Yoon Soo
Shim, Hyunbo
Kim, Sunghoon
author_facet Kim, Dae Gyu
Nguyen, Thi Thu Ha
Kwon, Nam Hoon
Sung, Junsik
Lim, Semi
Kang, Eun-Joo
Lee, Jihye
Seo, Woo Young
Kim, Arum
Chang, Yoon Soo
Shim, Hyunbo
Kim, Sunghoon
author_sort Kim, Dae Gyu
collection PubMed
description 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.
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spelling pubmed-73566292020-07-22 An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody Kim, Dae Gyu Nguyen, Thi Thu Ha Kwon, Nam Hoon Sung, Junsik Lim, Semi Kang, Eun-Joo Lee, Jihye Seo, Woo Young Kim, Arum Chang, Yoon Soo Shim, Hyunbo Kim, Sunghoon Biomolecules Article 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. MDPI 2020-05-27 /pmc/articles/PMC7356629/ /pubmed/32471182 http://dx.doi.org/10.3390/biom10060820 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Dae Gyu
Nguyen, Thi Thu Ha
Kwon, Nam Hoon
Sung, Junsik
Lim, Semi
Kang, Eun-Joo
Lee, Jihye
Seo, Woo Young
Kim, Arum
Chang, Yoon Soo
Shim, Hyunbo
Kim, Sunghoon
An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody
title An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody
title_full An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody
title_fullStr An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody
title_full_unstemmed An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody
title_short An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody
title_sort isoform of the oncogenic splice variant aimp2-dx2 detected by a novel monoclonal antibody
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356629/
https://www.ncbi.nlm.nih.gov/pubmed/32471182
http://dx.doi.org/10.3390/biom10060820
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