eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation
Translation initiation in protein synthesis regulated by eukaryotic initiation factors (eIFs) is a crucial step in controlling gene expression. eIF3a has been shown to regulate protein synthesis and cellular response to treatments by anticancer agents including cisplatin by regulating nucleotide exc...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00753/full |
| _version_ | 1818550711998218240 |
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| author | Rima Tumia Chao J. Wang Tianhan Dong Shijie Ma Jenny Beebe Juan Chen Zizheng Dong Jing-Yuan Liu Jian-Ting Zhang Jian-Ting Zhang |
| author_facet | Rima Tumia Chao J. Wang Tianhan Dong Shijie Ma Jenny Beebe Juan Chen Zizheng Dong Jing-Yuan Liu Jian-Ting Zhang Jian-Ting Zhang |
| author_sort | Rima Tumia |
| collection | DOAJ |
| description | Translation initiation in protein synthesis regulated by eukaryotic initiation factors (eIFs) is a crucial step in controlling gene expression. eIF3a has been shown to regulate protein synthesis and cellular response to treatments by anticancer agents including cisplatin by regulating nucleotide excision repair. In this study, we tested the hypothesis that eIF3a regulates the synthesis of proteins important for the repair of double-strand DNA breaks induced by ionizing radiation (IR). We found that eIF3a upregulation sensitized cellular response to IR while its downregulation caused resistance to IR. eIF3a increases IR-induced DNA damages and decreases non-homologous end joining (NHEJ) activity by suppressing the synthesis of NHEJ repair proteins. Furthermore, analysis of existing patient database shows that eIF3a expression associates with better overall survival of breast, gastric, lung, and ovarian cancer patients. These findings together suggest that eIF3a plays an important role in cellular response to DNA-damaging treatments by regulating the synthesis of DNA repair proteins and, thus, eIIF3a likely contributes to the outcome of cancer patients treated with DNA-damaging strategies including IR. |
| first_indexed | 2024-12-12T08:50:09Z |
| format | Article |
| id | doaj.art-2220767da4ce479ea9218ab217b228b2 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T08:50:09Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-2220767da4ce479ea9218ab217b228b22022-12-22T00:30:15ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-08-01810.3389/fcell.2020.00753554627eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing RadiationRima Tumia0Chao J. Wang1Tianhan Dong2Shijie Ma3Jenny Beebe4Juan Chen5Zizheng Dong6Jing-Yuan Liu7Jian-Ting Zhang8Jian-Ting Zhang9Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United StatesDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United StatesDepartment of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United StatesDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United StatesTranslation initiation in protein synthesis regulated by eukaryotic initiation factors (eIFs) is a crucial step in controlling gene expression. eIF3a has been shown to regulate protein synthesis and cellular response to treatments by anticancer agents including cisplatin by regulating nucleotide excision repair. In this study, we tested the hypothesis that eIF3a regulates the synthesis of proteins important for the repair of double-strand DNA breaks induced by ionizing radiation (IR). We found that eIF3a upregulation sensitized cellular response to IR while its downregulation caused resistance to IR. eIF3a increases IR-induced DNA damages and decreases non-homologous end joining (NHEJ) activity by suppressing the synthesis of NHEJ repair proteins. Furthermore, analysis of existing patient database shows that eIF3a expression associates with better overall survival of breast, gastric, lung, and ovarian cancer patients. These findings together suggest that eIF3a plays an important role in cellular response to DNA-damaging treatments by regulating the synthesis of DNA repair proteins and, thus, eIIF3a likely contributes to the outcome of cancer patients treated with DNA-damaging strategies including IR.https://www.frontiersin.org/article/10.3389/fcell.2020.00753/fulleukaryotic initiation factor 3a (eIF3a)DNA repairradiationresistancemRNA translationprotein synthesis |
| spellingShingle | Rima Tumia Chao J. Wang Tianhan Dong Shijie Ma Jenny Beebe Juan Chen Zizheng Dong Jing-Yuan Liu Jian-Ting Zhang Jian-Ting Zhang eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation Frontiers in Cell and Developmental Biology eukaryotic initiation factor 3a (eIF3a) DNA repair radiation resistance mRNA translation protein synthesis |
| title | eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation |
| title_full | eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation |
| title_fullStr | eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation |
| title_full_unstemmed | eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation |
| title_short | eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation |
| title_sort | eif3a regulation of nhej repair protein synthesis and cellular response to ionizing radiation |
| topic | eukaryotic initiation factor 3a (eIF3a) DNA repair radiation resistance mRNA translation protein synthesis |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00753/full |
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