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Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics
Translationally controlled tumor protein(TCTP) has been implicated in the regulation of apoptosis, DNA repair and drug resistance. However, the underlying molecular mechanisms are poorly defined. To better understand the molecular mechanisms underlying TCTP involved in cellular processes, we perform...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735297/ https://www.ncbi.nlm.nih.gov/pubmed/28846114 http://dx.doi.org/10.1038/onc.2017.289 |
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author | Li, Y Sun, H Zhang, C Liu, J Zhang, H Fan, F Everley, R A Ning, X Sun, Y Hu, J Liu, J Zhang, J Ye, W Qiu, X Dai, S Liu, B Xu, H Fu, S Gygi, S P Zhou, C |
author_facet | Li, Y Sun, H Zhang, C Liu, J Zhang, H Fan, F Everley, R A Ning, X Sun, Y Hu, J Liu, J Zhang, J Ye, W Qiu, X Dai, S Liu, B Xu, H Fu, S Gygi, S P Zhou, C |
author_sort | Li, Y |
collection | PubMed |
description | Translationally controlled tumor protein(TCTP) has been implicated in the regulation of apoptosis, DNA repair and drug resistance. However, the underlying molecular mechanisms are poorly defined. To better understand the molecular mechanisms underlying TCTP involved in cellular processes, we performed an affinity purification-based proteomic profiling to identify proteins interacting with TCTP in human cervical cancer HeLa cells. We found that a group of proteins involved in DNA repair are enriched in the potential TCTP interactome. Silencing TCTP by short hairpin RNA in breast carcinoma MCF-7 cells leads to the declined repair efficiency for DNA double-strand breaks on the GFP-Pem1 reporter gene by homologous recombination, the persistent activation and the prolonged retention of γH2AX and Rad51 foci following ionizing radiation. Reciprocal immunoprecipitations indicated that TCTP forms complexes with Rad51 in vivo, and the stability maintenance of Rad51 requires TCTP in MCF-7 cells under normal cell culture conditions. Moreover, inactivation of TCTP by sertraline treatment enhances UVC irradiation-induced apoptosis in MCF-7 cells, and causes sensitization to DNA-damaging drug etoposide and DNA repair inhibitor olaparib. Thus, we have identified an important role of TCTP in promoting DNA double-stand break repair via facilitating DNA homologous recombination processes and highlighted the great potential of TCTP as a drug target to enhance conventional chemotherapy for cancer patients with high levels of TCTP expression. |
format | Online Article Text |
id | pubmed-5735297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-57352972017-12-20 Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics Li, Y Sun, H Zhang, C Liu, J Zhang, H Fan, F Everley, R A Ning, X Sun, Y Hu, J Liu, J Zhang, J Ye, W Qiu, X Dai, S Liu, B Xu, H Fu, S Gygi, S P Zhou, C Oncogene Original Article Translationally controlled tumor protein(TCTP) has been implicated in the regulation of apoptosis, DNA repair and drug resistance. However, the underlying molecular mechanisms are poorly defined. To better understand the molecular mechanisms underlying TCTP involved in cellular processes, we performed an affinity purification-based proteomic profiling to identify proteins interacting with TCTP in human cervical cancer HeLa cells. We found that a group of proteins involved in DNA repair are enriched in the potential TCTP interactome. Silencing TCTP by short hairpin RNA in breast carcinoma MCF-7 cells leads to the declined repair efficiency for DNA double-strand breaks on the GFP-Pem1 reporter gene by homologous recombination, the persistent activation and the prolonged retention of γH2AX and Rad51 foci following ionizing radiation. Reciprocal immunoprecipitations indicated that TCTP forms complexes with Rad51 in vivo, and the stability maintenance of Rad51 requires TCTP in MCF-7 cells under normal cell culture conditions. Moreover, inactivation of TCTP by sertraline treatment enhances UVC irradiation-induced apoptosis in MCF-7 cells, and causes sensitization to DNA-damaging drug etoposide and DNA repair inhibitor olaparib. Thus, we have identified an important role of TCTP in promoting DNA double-stand break repair via facilitating DNA homologous recombination processes and highlighted the great potential of TCTP as a drug target to enhance conventional chemotherapy for cancer patients with high levels of TCTP expression. Nature Publishing Group 2017-12-14 2017-08-28 /pmc/articles/PMC5735297/ /pubmed/28846114 http://dx.doi.org/10.1038/onc.2017.289 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Original Article Li, Y Sun, H Zhang, C Liu, J Zhang, H Fan, F Everley, R A Ning, X Sun, Y Hu, J Liu, J Zhang, J Ye, W Qiu, X Dai, S Liu, B Xu, H Fu, S Gygi, S P Zhou, C Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics |
title | Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics |
title_full | Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics |
title_fullStr | Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics |
title_full_unstemmed | Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics |
title_short | Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics |
title_sort | identification of translationally controlled tumor protein in promotion of dna homologous recombination repair in cancer cells by affinity proteomics |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735297/ https://www.ncbi.nlm.nih.gov/pubmed/28846114 http://dx.doi.org/10.1038/onc.2017.289 |
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