Browsing by Author "Chen, Juan"

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    Corrigendum: eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation
    (Frontiers Media, 2021-01-07) Tumia, Rima; Wang, Chao J.; Dong, Tianhan; Ma, Shijie; Beebe, Jenny; Chen, Juan; Dong, Zizheng; Liu, Jing-Yuan; Zhang, Jian-Ting; Pharmacology and Toxicology, School of Medicine
    [This corrects the article DOI: 10.3389/fcell.2020.00753.].
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    eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation
    (Frontiers, 2020-08-19) Tumia, Rima; Wang, Chao J.; Dong, Tianhan; Ma, Shijie; Beebe, Jenny; Chen, Juan; Dong, Zizheng; Liu, Jing-Yuan; Zhang, Jian-Ting; Pharmacology and Toxicology, School of Medicine
    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.
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    Fluorescent protein tagged hepatitis B virus capsid protein with long glycine-serine linker that supports nucleocapsid formation
    (Elsevier, 2018-05) Chen, Jiang-Yan; Gan, Chun-yang; Cai, Xue-fei; Zhang, Wen-lu; Long, Quan-xin; Wei, Xia-fei; Hu, Yuan; Tang, Ni; Chen, Juan; Guo, Haito; Huang, Ai-long; Hu, Jie-li; Microbiology and Immunology, School of Medicine
    Fusion core proteins of Hepatitis B virus can be used to study core protein functions or capsid trafficking. A problem in constructing fusion core proteins is functional impairment of the individual domains in these fusion proteins, might due to structural interference. We reported a method to construct fusion proteins of Hepatitis B virus core protein (HBc) in which the functions of fused domains were partially kept. This method follows two principles: (1) fuse heterogeneous proteins at the N terminus of HBc; (2) use long Glycine-serine linkers between the two domains. Using EGFP and RFP as examples, we showed that long flexible G4S linkers can effectively separate the two domains in function. Among these fusion proteins constructed, GFP-G4S186-HBc and RFP-G4S47-HBc showed the best efficiency in rescuing the replication of an HBV replicon deficient in the core protein expression, though both of the two fusion proteins failed to support the formation of the relaxed circular DNA. These fluorescent protein-tagged HBcs might help study related to HBc or capsids tracking in cells.
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    Identification of Compounds Targeting Hepatitis B Virus Core Protein Dimerization through a Split Luciferase Complementation Assay
    (American Society for Microbiology, 2018-11-26) Wei, Xia-Fei; Gan, Chun-Yang; Cui, Jing; Luo, Ying-Ying; Cai, Xue-Fei; Yuan, Yi; Shen, Jing; Li, Zhi-Ying; Zhang, Wen-Lu; Long, Quan-Xin; Hu, Yuan; Chen, Juan; Tang, Ni; Guo, Haitao; Huang, Ai-Long; Hu, Jie-Li; Microbiology and Immunology, School of Medicine
    The capsid of the hepatitis B virus is an attractive antiviral target for developing therapies against chronic hepatitis B infection. Currently available core protein allosteric modulators (CpAMs) mainly affect one of the two major types of protein-protein interactions involved in the process of capsid assembly, namely, the interaction between the core dimers. Compounds targeting the interaction between two core monomers have not been rigorously screened due to the lack of screening models. We report here a cell-based assay in which the formation of core dimers is indicated by split luciferase complementation (SLC). Making use of this model, 2 compounds, Arbidol (umifenovir) and 20-deoxyingenol, were identified from a library containing 672 compounds as core dimerization regulators. Arbidol and 20-deoxyingenol inhibit the hepatitis B virus (HBV) DNA replication in vitro by decreasing and increasing the formation of core dimer and capsid, respectively. Our results provided a proof of concept for the cell model to be used to screen new agents targeting the step of core dimer and capsid formation.