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Mei-Ru Chen
Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei 100233, Taiwan

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Review
Published: 18 April 2021 in Viruses
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The nuclear envelope (NE) of eukaryotic cells has a highly structural architecture, comprising double lipid-bilayer membranes, nuclear pore complexes, and an underlying nuclear lamina network. The NE structure is held in place through the membrane-bound LINC (linker of nucleoskeleton and cytoskeleton) complex, spanning the inner and outer nuclear membranes. The NE functions as a barrier between the nucleus and cytoplasm and as a transverse scaffold for various cellular processes. Epstein–Barr virus (EBV) is a human pathogen that infects most of the world’s population and is associated with several well-known malignancies. Within the nucleus, the replicated viral DNA is packaged into capsids, which subsequently egress from the nucleus into the cytoplasm for tegumentation and final envelopment. There is increasing evidence that viral lytic gene expression or replication contributes to the pathogenesis of EBV. Various EBV lytic proteins regulate and modulate the nuclear envelope structure in different ways, especially the viral BGLF4 kinase and the nuclear egress complex BFRF1/BFRF2. From the aspects of nuclear membrane structure, viral components, and fundamental nucleocytoplasmic transport controls, this review summarizes our findings and recently updated information on NE structure modification and NE-related cellular processes mediated by EBV.

ACS Style

Chung-Pei Lee; Mei-Ru Chen. Conquering the Nuclear Envelope Barriers by EBV Lytic Replication. Viruses 2021, 13, 702 .

AMA Style

Chung-Pei Lee, Mei-Ru Chen. Conquering the Nuclear Envelope Barriers by EBV Lytic Replication. Viruses. 2021; 13 (4):702.

Chicago/Turabian Style

Chung-Pei Lee; Mei-Ru Chen. 2021. "Conquering the Nuclear Envelope Barriers by EBV Lytic Replication." Viruses 13, no. 4: 702.

Journal article
Published: 17 January 2020 in Journal of Virology
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Although Epstein-Barr virus (EBV) BFRF1 and BFLF2 are homologs of conserved viral nuclear egress complex (NEC) in all human herpesviruses, unique amino acid sequences and functions were identified in both proteins. In this study, the nuclear targeting and BFRF1-interacting domains were found within the N terminus of BFLF2. We showed that amino acids (aa) 82 to 106 are the major region required for BFLF2 to interact with BFRF1. However, the coimmunoprecipitation (Co-IP) data and glutathione transferase (GST) pulldown experiments revealed that multiple regions of both proteins contribute to reciprocal interactions. Different from the canonical nuclear localization signal (NLS) in other herpes viral homologs, BFLF2 contains a novel importin-dependent nuclear localization signal, including R47, K50, and R52 and several neighboring discontinuous arginine and histidine residues. Using a bacmid complementation system, we show that both the nuclear targeting and the novel nuclear localization signal within aa 82 to 106 of BFLF2 are required for virion secretion.

ACS Style

Yu-Ching Dai; Yen-Tzu Liao; Yi-Ting Juan; Yi-Ying Cheng; Mei-Tzu Su; Yu-Zhen Su; Hung-Chun Liu; Ching-Hwa Tsai; Chung-Pei Lee; Mei-Ru Chen. The Novel Nuclear Targeting and BFRF1-Interacting Domains of BFLF2 Are Essential for Efficient Epstein-Barr Virus Virion Release. Journal of Virology 2020, 94, 1 .

AMA Style

Yu-Ching Dai, Yen-Tzu Liao, Yi-Ting Juan, Yi-Ying Cheng, Mei-Tzu Su, Yu-Zhen Su, Hung-Chun Liu, Ching-Hwa Tsai, Chung-Pei Lee, Mei-Ru Chen. The Novel Nuclear Targeting and BFRF1-Interacting Domains of BFLF2 Are Essential for Efficient Epstein-Barr Virus Virion Release. Journal of Virology. 2020; 94 (3):1.

Chicago/Turabian Style

Yu-Ching Dai; Yen-Tzu Liao; Yi-Ting Juan; Yi-Ying Cheng; Mei-Tzu Su; Yu-Zhen Su; Hung-Chun Liu; Ching-Hwa Tsai; Chung-Pei Lee; Mei-Ru Chen. 2020. "The Novel Nuclear Targeting and BFRF1-Interacting Domains of BFLF2 Are Essential for Efficient Epstein-Barr Virus Virion Release." Journal of Virology 94, no. 3: 1.

Journal article
Published: 01 May 2017 in Journal of Virology
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During the lytic phase of Epstein-Barr virus (EBV), binding of the transactivator Zta to the origin of lytic replication (oriLyt) and the BHLF1 transcript, forming a stable RNA-DNA hybrid, is required to initiate viral DNA replication. EBV-encoded viral DNA replication proteins form complexes to amplify viral DNA. BMRF1, the viral DNA polymerase accessory factor, is essential for lytic DNA replication and also known as a transcriptional regulator of the expression of BHLF1 and BALF2 (single-stranded DNA [ssDNA]-binding protein). In order to determine systematically how BMRF1 regulates viral transcription, a BMRF1 knockout bacmid was generated to analyze viral gene expression using a viral DNA microarray. We found that a subset of Rta-responsive late genes, including BcLF1, BLLF1, BLLF2, and BDLF3, were downregulated in cells harboring a BMRF1 knockout EBV bacmid (p2089ΔBMRF1). In reporter assays, BMRF1 appears to transactivate a subset of viral late promoters through distinct pathways. BMRF1 activates the BDLF3 promoter in an SP1-dependent manner. Notably, BMRF1 associates with the transcriptional regulator BRG1 in EBV-reactivated cells. BMRF1-mediated transactivation activities on the BcLF1 and BLLF1 promoters were attenuated by knockdown of BRG1. In BRG1-depleted EBV-reactivated cells, BcLF1 and BLLF1 transcripts were reduced in number, resulting in reduced virion secretion. BMRF1 and BRG1 bound to the adjacent upstream regions of the BcLF1 and BLLF1 promoters, and depletion of BRG1 attenuated the recruitment of BMRF1 onto both promoters, suggesting that BRG1 is involved in BMRF1-mediated regulation of these two genes. Overall, we reveal a novel pathway by which BMRF1 can regulate viral promoters through interaction with BRG1. IMPORTANCE The cascade of viral gene expression during Epstein-Barr virus (EBV) replication is exquisitely regulated by the coordination of the viral DNA replication machinery and cellular factors. Upon lytic replication, the EBV immediate early proteins Zta and Rta turn on the expression of early proteins that assemble into viral DNA replication complexes. The DNA polymerase accessory factor, BMRF1, also is known to transactivate early gene expression through its interaction with SP1 or Zta on specific promoters. Through a global analysis, we demonstrate that BMRF1 also turns on a subset of Rta-regulated, late structural gene promoters. Searching for BMRF1-interacting cellular partners revealed that the SWI/SNF chromatin modifier BRG1 contributes to BMRF1-mediated transactivation of a subset of late promoters through protein-protein interaction and viral chromatin binding. Our findings indicate that BMRF1 regulates the expression of more viral genes than thought previously through distinct viral DNA replication-independent mechanisms.

ACS Style

Mei-Tzu Su; Ya-Ting Wang; Yen-Ju Chen; Su-Fang Lin; Ching-Hwa Tsai; Mei-Ru Chen. The SWI/SNF Chromatin Regulator BRG1 Modulates the Transcriptional Regulatory Activity of the Epstein-Barr Virus DNA Polymerase Processivity Factor BMRF1. Journal of Virology 2017, 91, e02114-16 .

AMA Style

Mei-Tzu Su, Ya-Ting Wang, Yen-Ju Chen, Su-Fang Lin, Ching-Hwa Tsai, Mei-Ru Chen. The SWI/SNF Chromatin Regulator BRG1 Modulates the Transcriptional Regulatory Activity of the Epstein-Barr Virus DNA Polymerase Processivity Factor BMRF1. Journal of Virology. 2017; 91 (9):e02114-16.

Chicago/Turabian Style

Mei-Tzu Su; Ya-Ting Wang; Yen-Ju Chen; Su-Fang Lin; Ching-Hwa Tsai; Mei-Ru Chen. 2017. "The SWI/SNF Chromatin Regulator BRG1 Modulates the Transcriptional Regulatory Activity of the Epstein-Barr Virus DNA Polymerase Processivity Factor BMRF1." Journal of Virology 91, no. 9: e02114-16.

Journal article
Published: 21 December 2016 in Journal of Vegetation Science
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QuestionQuantifying the duration and drivers of seedling persistence is critical for understanding seedling dynamics and species co-existence in plant communities. In this study, we incorporated data from multiple seedling censuses to characterize patterns of seedling persistence in a tropical karst forest. Specifically, we evaluated the effects of density dependence, habitat heterogeneity and recruitment timing on seedling persistence.LocationA tropical karst forest in Taiwan.MethodsUsing data from 144 seedling plots censused every 3 mo from 2007 to 2012, we examined persistence times of 6399 seedlings of 36 species. Seedling survival was estimated by the Kaplan–Meier method. Mixed effects Cox models were used to identify significant biotic (i.e. initial height, conspecific and heterospecific seedling and adult densities) and abiotic (i.e. mean elevation, convexity, slope, effective soil depth and recruitment time) drivers of seedling persistence at the community, guild and species levels.ResultsAt the community level, newly recruited seedlings had a median survival time of 6 mo. Median survival time was higher for seedlings in the shade-tolerant guild compared to seedlings in the shade-intolerant guild (9 vs 3 mo). When all species were analysed together, seedling persistence significantly increased with increasing initial size and soil depth and significantly decreased with increasing density of conspecific and heterospecific seedling neighbours. Drivers of seedling persistence tended to be guild and species specific, however negative effects of conspecific seedling neighbours were consistently detected in all models, indicating strong and pervasive conspecific negative density dependence. Significant effects of recruitment time, soil depth and convexity were revealed by guild- and species-specific models, suggesting abiotic niche differences.ConclusionsThis study highlights the importance of multiple ecological processes for seedling persistence. Both abiotic and biotic factors may play an important role in species co-existence in this forest via niche partitioning and negative density dependence. Among these factors, negative conspecific density dependence had the strongest and most consistent effect. In addition, soil depth played a key role in shaping seedling regeneration, likely through effects of soil moisture. Overall, this study contributes to a better understanding of the ecology of karst forests. Analysing seedling persistence in karst forest expands our general understanding of forest dynamics and species co-existence in tropical forests as a whole, especially at sites with high spatial heterogeneity.

ACS Style

Yi‐Ching Lin; Liza S. Comita; Daniel Johnson; Mei‐Ru Chen; Shu‐Hui Wu. Biotic vs abiotic drivers of seedling persistence in a tropical karst forest. Journal of Vegetation Science 2016, 28, 206 -217.

AMA Style

Yi‐Ching Lin, Liza S. Comita, Daniel Johnson, Mei‐Ru Chen, Shu‐Hui Wu. Biotic vs abiotic drivers of seedling persistence in a tropical karst forest. Journal of Vegetation Science. 2016; 28 (1):206-217.

Chicago/Turabian Style

Yi‐Ching Lin; Liza S. Comita; Daniel Johnson; Mei‐Ru Chen; Shu‐Hui Wu. 2016. "Biotic vs abiotic drivers of seedling persistence in a tropical karst forest." Journal of Vegetation Science 28, no. 1: 206-217.

Journal article
Published: 15 October 2016 in Journal of Virology
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The cellular endosomal sorting complex required for transport (ESCRT) was recently found to mediate important morphogenesis processes at the nuclear envelope (NE). We previously showed that the Epstein-Barr virus (EBV) BFRF1 protein recruits the ESCRT-associated protein Alix to modulate NE structure and promote EBV nuclear egress. Here, we uncover new cellular factors and mechanisms involved in this process. BFRF1-induced NE vesicles are similar to those observed following EBV reactivation. BFRF1 is ubiquitinated, and elimination of possible ubiquitination by either lysine mutations or fusion of a deubiquitinase hampers NE-derived vesicle formation and virus maturation. While it interacts with multiple Nedd4-like ubiquitin ligases, BFRF1 preferentially binds Itch ligase. We show that Itch associates with Alix and BFRF1 and is required for BFRF1-induced NE vesicle formation. Our data demonstrate that Itch, ubiquitin, and Alix control the BFRF1-mediated modulation of the NE and EBV maturation, uncovering novel regulatory mechanisms of nuclear egress of viral nucleocapsids. IMPORTANCE The nuclear envelope (NE) of eukaryotic cells not only serves as a transverse scaffold for cellular processes, but also as a natural barrier for most DNA viruses that assemble their nucleocapsids in the nucleus. Previously, we showed that the cellular endosomal sorting complex required for transport (ESCRT) machinery is required for the nuclear egress of EBV. Here, we further report the molecular interplay among viral BFRF1, the ESCRT adaptor Alix, and the ubiquitin ligase Itch. We found that BFRF1-induced NE vesicles are similar to those observed following EBV reactivation. The lysine residues and the ubiquitination of BFRF1 regulate the formation of BFRF1-induced NE-derived vesicles and EBV maturation. During the process, a ubiquitin ligase, Itch, preferably associates with BFRF1 and is required for BFRF1-induced NE vesicle formation. Therefore, our data indicate that Itch, ubiquitin, and Alix control the BFRF1-mediated modulation of the NE, suggesting novel regulatory mechanisms for ESCRT-mediated NE modulation.

ACS Style

Chung-Pei Lee; Guan-Ting Liu; Hsiu-Ni Kung; Po-Ting Liu; Yen-Tzu Liao; Lu-Ping Chow; Ling-Shih Chang; Yu-Hsin Chang; Chou-Wei Chang; Wen-Chi Shu; Annie Angers; Antonella Farina; Su-Fang Lin; Ching-Hwa Tsai; Fadila Bouamr; Mei-Ru Chen. The Ubiquitin Ligase Itch and Ubiquitination Regulate BFRF1-Mediated Nuclear Envelope Modification for Epstein-Barr Virus Maturation. Journal of Virology 2016, 90, 8994 -9007.

AMA Style

Chung-Pei Lee, Guan-Ting Liu, Hsiu-Ni Kung, Po-Ting Liu, Yen-Tzu Liao, Lu-Ping Chow, Ling-Shih Chang, Yu-Hsin Chang, Chou-Wei Chang, Wen-Chi Shu, Annie Angers, Antonella Farina, Su-Fang Lin, Ching-Hwa Tsai, Fadila Bouamr, Mei-Ru Chen. The Ubiquitin Ligase Itch and Ubiquitination Regulate BFRF1-Mediated Nuclear Envelope Modification for Epstein-Barr Virus Maturation. Journal of Virology. 2016; 90 (20):8994-9007.

Chicago/Turabian Style

Chung-Pei Lee; Guan-Ting Liu; Hsiu-Ni Kung; Po-Ting Liu; Yen-Tzu Liao; Lu-Ping Chow; Ling-Shih Chang; Yu-Hsin Chang; Chou-Wei Chang; Wen-Chi Shu; Annie Angers; Antonella Farina; Su-Fang Lin; Ching-Hwa Tsai; Fadila Bouamr; Mei-Ru Chen. 2016. "The Ubiquitin Ligase Itch and Ubiquitination Regulate BFRF1-Mediated Nuclear Envelope Modification for Epstein-Barr Virus Maturation." Journal of Virology 90, no. 20: 8994-9007.

Journal article
Published: 14 May 2016 in Nephrology Dialysis Transplantation
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Introduction and Aims: Previous observational studies suggest an association between moderate alcohol consumption and a lower risk of cardiovascular disease. However, the associations between alcohol consumption and the change in renal function remain inconclusive. This study aimed to assess the effects of alcohol consumption on the change in glomerular filtration rate in a seven year cohort study.

ACS Style

Hon-Yen Wu; Hung-Ju Lin; Mei-Ru Chen; Yu-Sen Peng; Yu-Kang Tu; Kuan-Yu Hung; Kuo-Liong Chien. SP263EFFECTS OF ALCOHOL CONSUMPTION ON CHRONIC KIDNEY DISEASE: A SEVEN YEAR COHORT STUDY. Nephrology Dialysis Transplantation 2016, 31, i175 -i175.

AMA Style

Hon-Yen Wu, Hung-Ju Lin, Mei-Ru Chen, Yu-Sen Peng, Yu-Kang Tu, Kuan-Yu Hung, Kuo-Liong Chien. SP263EFFECTS OF ALCOHOL CONSUMPTION ON CHRONIC KIDNEY DISEASE: A SEVEN YEAR COHORT STUDY. Nephrology Dialysis Transplantation. 2016; 31 (suppl_1):i175-i175.

Chicago/Turabian Style

Hon-Yen Wu; Hung-Ju Lin; Mei-Ru Chen; Yu-Sen Peng; Yu-Kang Tu; Kuan-Yu Hung; Kuo-Liong Chien. 2016. "SP263EFFECTS OF ALCOHOL CONSUMPTION ON CHRONIC KIDNEY DISEASE: A SEVEN YEAR COHORT STUDY." Nephrology Dialysis Transplantation 31, no. suppl_1: i175-i175.

Journal article
Published: 01 January 2016 in Journal of Cleaner Production
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[[abstract]]This study was conducted in a real-scale iron ore sinter plant for reducing emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from the iron ore sintering process via the adjustment of its sinter raw mix. Based on operating condition of the selected plant, four experimental campaigns of Cref (currently used raw mix, served as the reference), CH (modified from Cref, with a 15% increase in hematite but 15% decrease in limonite), CH,EP (modified from CH, without electrostatic precipitator (EP) and blast furnace (BF) flue dusts), and CH,EP,W (modified from CH,EP, with a 0.5 wt% increase in water content) were chosen. For each experimental campaign, three replicate samples of PCDD/Fs were collected from the flue gases, and the sinter productivity and sinter strength were measured simultaneously. In comparison with Cref, the most significant reductions in PCDD/F and I-TEQ emissions was found in CH,EP (=68% and 76%, respectively), and the main reduction was found in PCDFs (54–76% decrease). CH could reduce emissions of PCDD/Fs and I-TEQ by 47% and 51%, respectively. But the addition of water contents (i.e., CH,EP,W) did not result in further reductions. Since sinter productivity and sinter strength of all experimental campaigns were quite similar, CH,EP could be a promising raw mix for reducing PCDD/F emissions from the sintering process

ACS Style

Yu-Cheng Chen; Yu-Chieh Kuo; Mei-Ru Chen; Ying-Fang Wang; Ching-Hwa Chen; Ming-Yeng Lin; ChungSik Yoon; Perng-Jy Tsai. Reducing polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) emissions from a real-scale iron ore sinter plant by adjusting its sinter raw mix. Journal of Cleaner Production 2016, 112, 1184 -1189.

AMA Style

Yu-Cheng Chen, Yu-Chieh Kuo, Mei-Ru Chen, Ying-Fang Wang, Ching-Hwa Chen, Ming-Yeng Lin, ChungSik Yoon, Perng-Jy Tsai. Reducing polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) emissions from a real-scale iron ore sinter plant by adjusting its sinter raw mix. Journal of Cleaner Production. 2016; 112 ():1184-1189.

Chicago/Turabian Style

Yu-Cheng Chen; Yu-Chieh Kuo; Mei-Ru Chen; Ying-Fang Wang; Ching-Hwa Chen; Ming-Yeng Lin; ChungSik Yoon; Perng-Jy Tsai. 2016. "Reducing polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) emissions from a real-scale iron ore sinter plant by adjusting its sinter raw mix." Journal of Cleaner Production 112, no. : 1184-1189.

Journal article
Published: 01 January 2016 in Aerosol and Air Quality Research
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ACS Style

Hsiu-Ling Chen; Yu-Chun Wu; Mei-Ru Chen; Jui-Shu Chou; Shu-Kai Zheng; Jia-Zhong Hou. Risk Assessment of PAH Exposure Involving Metal Working Fluids in Fastener Manufacturing Industries. Aerosol and Air Quality Research 2016, 16, 3212 -3221.

AMA Style

Hsiu-Ling Chen, Yu-Chun Wu, Mei-Ru Chen, Jui-Shu Chou, Shu-Kai Zheng, Jia-Zhong Hou. Risk Assessment of PAH Exposure Involving Metal Working Fluids in Fastener Manufacturing Industries. Aerosol and Air Quality Research. 2016; 16 (12):3212-3221.

Chicago/Turabian Style

Hsiu-Ling Chen; Yu-Chun Wu; Mei-Ru Chen; Jui-Shu Chou; Shu-Kai Zheng; Jia-Zhong Hou. 2016. "Risk Assessment of PAH Exposure Involving Metal Working Fluids in Fastener Manufacturing Industries." Aerosol and Air Quality Research 16, no. 12: 3212-3221.

Journal article
Published: 01 July 2015 in Virology
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Epstein Barr virus (EBV) uses various strategies to manipulate host cytokine production in favor of the survival of infected B-cells. Microarray and cytokine protein array assays revealed that tissue inhibitor of metalloproteinase-1 (TIMP-1) was significantly up-regulated in EBV-infected primary B cells and maintained in abundance in EBV-immortalized lymphoblastoid cell lines (LCLs). TIMP-1 plays critical roles in extracellular matrix homeostasis and regulates signaling pathways. In this study, we demonstrated that the EBV-encoded immediate early lytic protein, Zta, upregulates mainly TIMP-1 expression by binding to the AP-1 site within the TIMP-1 promoter. Moreover, knockdown of TIMP-1 expression promoted cisplastin and cold shock-induced death of LCLs. This study provides a mechanistic link between EBV-induced TIMP-1 expression and its impact on LCL survival.

ACS Style

Sue-Jane Lin; Shao-Wen Wu; Ya-Ching Chou; Jiun-Han Lin; Ya-Chi Huang; Mei-Ru Chen; Nianhan Ma; Ching-Hwa Tsai. Novel expression and regulation of TIMP-1 in Epstein Barr virus-infected cells and its impact on cell survival. Virology 2015, 481, 24 -33.

AMA Style

Sue-Jane Lin, Shao-Wen Wu, Ya-Ching Chou, Jiun-Han Lin, Ya-Chi Huang, Mei-Ru Chen, Nianhan Ma, Ching-Hwa Tsai. Novel expression and regulation of TIMP-1 in Epstein Barr virus-infected cells and its impact on cell survival. Virology. 2015; 481 ():24-33.

Chicago/Turabian Style

Sue-Jane Lin; Shao-Wen Wu; Ya-Ching Chou; Jiun-Han Lin; Ya-Chi Huang; Mei-Ru Chen; Nianhan Ma; Ching-Hwa Tsai. 2015. "Novel expression and regulation of TIMP-1 in Epstein Barr virus-infected cells and its impact on cell survival." Virology 481, no. : 24-33.

Journal article
Published: 02 April 2015 in Blood
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Key PointsEBV LMP2A alters B-cell gene expression; E47 and PU.1 are repressed by LMP2A, resulting in downregulation of MHC class II expression.

ACS Style

Jiun-Han Lin; Ju-Yin Lin; Ya-Ching Chou; Mei-Ru Chen; Te-Huei Yeh; Chung-Wu Lin; Sue-Jane Lin; Ching-Hwa Tsai. Epstein-Barr virus LMP2A suppresses MHC class II expression by regulating the B-cell transcription factors E47 and PU.1. Blood 2015, 125, 2228 -2238.

AMA Style

Jiun-Han Lin, Ju-Yin Lin, Ya-Ching Chou, Mei-Ru Chen, Te-Huei Yeh, Chung-Wu Lin, Sue-Jane Lin, Ching-Hwa Tsai. Epstein-Barr virus LMP2A suppresses MHC class II expression by regulating the B-cell transcription factors E47 and PU.1. Blood. 2015; 125 (14):2228-2238.

Chicago/Turabian Style

Jiun-Han Lin; Ju-Yin Lin; Ya-Ching Chou; Mei-Ru Chen; Te-Huei Yeh; Chung-Wu Lin; Sue-Jane Lin; Ching-Hwa Tsai. 2015. "Epstein-Barr virus LMP2A suppresses MHC class II expression by regulating the B-cell transcription factors E47 and PU.1." Blood 125, no. 14: 2228-2238.

Journal article
Published: 25 March 2015 in Journal of Virology
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Epstein-Barr virus (EBV), an oncogenic herpesvirus, has the potential to immortalize primary B cells into lymphoblastoid cell lines (LCLs)in vitro. During immortalization, several EBV products induce cytokines or chemokines, and most of these are required for the proliferation of LCLs. Interleukin-32 (IL-32), a recently discovered proinflammatory cytokine, is upregulated after EBV infection, and this upregulation is detectable in all LCLs tested. EBV latent membrane protein 1 (LMP1) is responsible for inducing IL-32 expression at the mRNA and protein levels. Mechanistically, we showed that this LMP1 induction is provided by the p65 subunit of NF-κB, which binds to and activates the IL-32 promoter. Furthermore, the short hairpin RNA (shRNA)-mediated depletion of endogenous LMP1 and p65 in LCLs suppressed IL-32 expression, further suggesting that LMP1 is the key factor that stimulates IL-32 in LCLs via the NF-κB p65 pathway. Functionally, knockdown of IL-32 in LCLs elicits viral reactivation and affects cytokine expression, but it has no impact on cell proliferation and apoptosis. Of note, we reveal the mechanism whereby IL-32 is involved in the maintenance of EBV viral latency by inactivation of Zta promoter activity. This atypical cytoplasmic IL-32 hijacks the Zta activator protein kinase Cδ (PKCδ) and inhibits its translocation from the cytoplasm to the nucleus, where PKCδ binds to the Zta promoter and activates lytic cycle progression. These novel findings reveal that IL-32 is involved in the maintenance of EBV latency in LCLs. This finding may provide new information to explain how EBV maintains latency, in addition to viral chromatin structure and epigenetic modification.IMPORTANCEEBV persists in two states, latency and lytic replication, which is a unique characteristic of human infections. So far, little is known about how herpesviruses maintain latency in particular tissues or cell types. EBV is an excellent model to study this question because more than 90% of people are latently infected. EBV can immortalize primary B cells into lymphoblastoid cell linesin vitro. Expression of IL-32, a novel atypical cytoplasmic proinflammatory cytokine, increased after infection. The expression of IL-32 was controlled by LMP1. In investigating the regulatory mechanism, we demonstrated that the p65 subunit of NF-κB is required for this upregulation. Of note, the important biological activity of IL-32 was to trap protein kinase Cδ in the cytoplasm and prevent it from binding to the Zta promoter, which is the key event for EBV reaction. So, the expression of LMP1-induced IL-32 plays a role in the maintenance of EBV latency.

ACS Style

Kun-Yi Lai; Ya-Ching Chou; Jiun-Han Lin; Yi Liu; Kai-Min Lin; Shin-Lian Doong; Mei-Ru Chen; Te-Huei Yeh; Sue-Jane Lin; Ching-Hwa Tsai. Maintenance of Epstein-Barr Virus Latent Status by a Novel Mechanism, Latent Membrane Protein 1-Induced Interleukin-32, via the Protein Kinase Cδ Pathway. Journal of Virology 2015, 89, 5968 -5980.

AMA Style

Kun-Yi Lai, Ya-Ching Chou, Jiun-Han Lin, Yi Liu, Kai-Min Lin, Shin-Lian Doong, Mei-Ru Chen, Te-Huei Yeh, Sue-Jane Lin, Ching-Hwa Tsai. Maintenance of Epstein-Barr Virus Latent Status by a Novel Mechanism, Latent Membrane Protein 1-Induced Interleukin-32, via the Protein Kinase Cδ Pathway. Journal of Virology. 2015; 89 (11):5968-5980.

Chicago/Turabian Style

Kun-Yi Lai; Ya-Ching Chou; Jiun-Han Lin; Yi Liu; Kai-Min Lin; Shin-Lian Doong; Mei-Ru Chen; Te-Huei Yeh; Sue-Jane Lin; Ching-Hwa Tsai. 2015. "Maintenance of Epstein-Barr Virus Latent Status by a Novel Mechanism, Latent Membrane Protein 1-Induced Interleukin-32, via the Protein Kinase Cδ Pathway." Journal of Virology 89, no. 11: 5968-5980.

Journal article
Published: 15 December 2014 in Nature Communications
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EGFR overexpression plays an important oncogenic role in cancer. Regular EGFR protein levels are increased in cancer cells and the receptor then becomes constitutively active. However, downstream signals generated by constitutively activated EGFR are unknown. Here we report that the overexpressed EGFR oscillates between two distinct and mutually exclusive modes of signaling. Constitutive or non-canonical EGFR signaling activates the transcription factor IRF3 leading to expression of IFI27, IFIT1, and TRAIL. Ligand-mediated activation of EGFR switches off IRF3 dependent transcription, activates canonical ERK and Akt signals, and confers sensitivity to chemotherapy and virus-induced cell death. Mechanistically, the distinct downstream signals result from a switch of EGFR associated proteins. EGFR constitutively complexes with IRF3 and TBK1 leading to TBK1 and IRF3 phosphorylation. Addition of EGF dissociates TBK1, IRF3, and EGFR leading to a loss of IRF3 activity, Shc-EGFR association and ERK activation. Finally, we provide evidence for non-canonical EGFR signaling in glioblastoma.

ACS Style

Sharmistha Chakraborty; Li Li; Vineshkumar Thidil Puliyappadamba; Gao Guo; Kimmo J. Hatanpaa; Bruce Mickey; Rhonda F. Souza; Peggy Vo; Joachim Herz; Mei-Ru Chen; David A. Boothman; Tej K. Pandita; David H. Wang; Ganes C. Sen; Amyn A. Habib. Constitutive and ligand-induced EGFR signalling triggers distinct and mutually exclusive downstream signalling networks. Nature Communications 2014, 5, 5811 -5811.

AMA Style

Sharmistha Chakraborty, Li Li, Vineshkumar Thidil Puliyappadamba, Gao Guo, Kimmo J. Hatanpaa, Bruce Mickey, Rhonda F. Souza, Peggy Vo, Joachim Herz, Mei-Ru Chen, David A. Boothman, Tej K. Pandita, David H. Wang, Ganes C. Sen, Amyn A. Habib. Constitutive and ligand-induced EGFR signalling triggers distinct and mutually exclusive downstream signalling networks. Nature Communications. 2014; 5 (1):5811-5811.

Chicago/Turabian Style

Sharmistha Chakraborty; Li Li; Vineshkumar Thidil Puliyappadamba; Gao Guo; Kimmo J. Hatanpaa; Bruce Mickey; Rhonda F. Souza; Peggy Vo; Joachim Herz; Mei-Ru Chen; David A. Boothman; Tej K. Pandita; David H. Wang; Ganes C. Sen; Amyn A. Habib. 2014. "Constitutive and ligand-induced EGFR signalling triggers distinct and mutually exclusive downstream signalling networks." Nature Communications 5, no. 1: 5811-5811.

Journal article
Published: 19 November 2014 in Journal of Virology
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BGLF4 kinase, the only Ser/Thr protein kinase encoded by the Epstein-Barr virus (EBV) genome, phosphorylates multiple viral and cellular substrates to optimize the cellular environment for viral DNA replication and the nuclear egress of nucleocapsids. Previously, we found that nuclear targeting of BGLF4 is through direct interaction with the FG repeat-containing nucleoporins (FG-Nups) Nup62 and Nup153 independently of cytosolic transport factors. Here, we investigated the regulatory effects of BGLF4 on the structure and biological functions of the nuclear pore complex (NPC). In EBV-positive NA cells, the distribution of FG-Nups was modified during EBV reactivation. In transfected cells, BGLF4 changed the staining pattern of Nup62 and Nup153 in a kinase activity-dependent manner. Detection with anti-phospho-Ser/Thr-Pro MPM-2 antibody demonstrated that BGLF4 induced the phosphorylation of Nup62 and Nup153. The nuclear targeting of importin β was attenuated in the presence of BGLF4, leading to inhibition of canonical nuclear localization signal (NLS)-mediated nuclear import. Anin vitronuclear import assay revealed that BGLF4 induced the nuclear import of larger molecules. Notably, we found that BGLF4 promoted the nuclear import of several non-NLS-containing EBV proteins, including the viral DNA-replicating enzymes BSLF1, BBLF2/3, and BBLF4 and the major capsid protein (VCA), in cotransfected cells. The data presented here suggest that BGLF4 interferes with the normal functions of Nup62 and Nup153 and preferentially helps the nuclear import of viral proteins for viral DNA replication and assembly. In addition, the nuclear import-promoting activity was found in cells expressing the BGLF4 homologs of another two gammaherpesviruses but not those from alpha- and betaherpesviruses.IMPORTANCEDuring lytic replication, many EBV genome-encoded proteins need to be transported into the nucleus, not only for viral DNA replication but also for the assembly of nucleocapsids. Because nuclear pore complexes are effective gateways that control nucleocytoplasmic traffic, most EBV proteins without canonical NLSs are retained in the cytoplasm until they form complexes with their NLS-containing partners for nuclear targeting. In this study, we found that EBV BGLF4 protein kinase interacts with the Nup62 and Nup153 and induces the redistribution of FG-Nups. BGLF4 modulates the function of the NPC to inhibit the nuclear import of host NLS-containing proteins. Simultaneously, the nuclear import of non-NLS-containing EBV lytic proteins was enhanced, possibly through phosphorylation of Nup62 and Nup153, nuclear pore dilation, or microtubule reorganization. Overall, our data suggest that BGLF4-induced modification of nuclear pore transport may block nuclear targeting of cellular proteins and increase the import of viral proteins to promote viral lytic replication.

ACS Style

Chou-Wei Chang; Chung-Pei Lee; Mei-Tzu Su; Ching-Hwa Tsai; Mei-Ru Chen. BGLF4 Kinase Modulates the Structure and Transport Preference of the Nuclear Pore Complex To Facilitate Nuclear Import of Epstein-Barr Virus Lytic Proteins. Journal of Virology 2014, 89, 1703 -1718.

AMA Style

Chou-Wei Chang, Chung-Pei Lee, Mei-Tzu Su, Ching-Hwa Tsai, Mei-Ru Chen. BGLF4 Kinase Modulates the Structure and Transport Preference of the Nuclear Pore Complex To Facilitate Nuclear Import of Epstein-Barr Virus Lytic Proteins. Journal of Virology. 2014; 89 (3):1703-1718.

Chicago/Turabian Style

Chou-Wei Chang; Chung-Pei Lee; Mei-Tzu Su; Ching-Hwa Tsai; Mei-Ru Chen. 2014. "BGLF4 Kinase Modulates the Structure and Transport Preference of the Nuclear Pore Complex To Facilitate Nuclear Import of Epstein-Barr Virus Lytic Proteins." Journal of Virology 89, no. 3: 1703-1718.

Journal article
Published: 28 May 2014 in Journal of Virology
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Epstein-Barr virus (EBV) BKRF3 shares sequence homology with members of the uracil-N-glycosylase (UNG) protein family and has DNA glycosylase activity. Here, we explored how BKRF3 participates in the DNA replication complex and contributes to viral DNA replication. Exogenously expressed Flag-BKRF3 was distributed mostly in the cytoplasm, whereas BKRF3 was translocated into the nucleus and colocalized with the EBV DNA polymerase BALF5 in the replication compartment during EBV lytic replication. The expression level of BKRF3 increased gradually during viral replication, coupled with a decrease of cellular UNG2, suggesting BKRF3 enzyme activity compensates for UNG2 and ensures the fidelity of viral DNA replication. In immunoprecipitation-Western blotting, BKRF3 was coimmunoprecipitated with BALF5, the polymerase processivity factor BMRF1, and the immediate-early transactivator Rta. Coexpression of BMRF1 appeared to facilitate the nuclear targeting of BKRF3 in immunofluorescence staining. Residues 164 to 255 of BKRF3 were required for interaction with Rta and BALF5, whereas residues 81 to 166 of BKRF3 were critical for BMRF1 interaction in glutathione S-transferase (GST) pulldown experiments. Viral DNA replication was defective in cells harboring BKRF3 knockout EBV bacmids. In complementation assays, the catalytic mutant BKRF3(Q90L,D91N) restored viral DNA replication, whereas the leucine loop mutant BKRF3(H213L) only partially rescued viral DNA replication, coupled with a reduced ability to interact with the viral DNA polymerase and Rta. Our data suggest that BKRF3 plays a critical role in viral DNA synthesis predominantly through its interactions with viral proteins in the DNA replication compartment, while its enzymatic activity may be supplementary for uracil DNA glycosylase (UDG) function during virus replication.

ACS Style

Mei-Tzu Su; I.-H. Liu; Chia-Wei Wu; Shu-Ming Chang; Ching-Hwa Tsai; Pei-Wen Yang; Yu-Chia Chuang; Chung-Pei Lee; Mei-Ru Chen. Uracil DNA Glycosylase BKRF3 Contributes to Epstein-Barr Virus DNA Replication through Physical Interactions with Proteins in Viral DNA Replication Complex. Journal of Virology 2014, 88, 8883 -8899.

AMA Style

Mei-Tzu Su, I.-H. Liu, Chia-Wei Wu, Shu-Ming Chang, Ching-Hwa Tsai, Pei-Wen Yang, Yu-Chia Chuang, Chung-Pei Lee, Mei-Ru Chen. Uracil DNA Glycosylase BKRF3 Contributes to Epstein-Barr Virus DNA Replication through Physical Interactions with Proteins in Viral DNA Replication Complex. Journal of Virology. 2014; 88 (16):8883-8899.

Chicago/Turabian Style

Mei-Tzu Su; I.-H. Liu; Chia-Wei Wu; Shu-Ming Chang; Ching-Hwa Tsai; Pei-Wen Yang; Yu-Chia Chuang; Chung-Pei Lee; Mei-Ru Chen. 2014. "Uracil DNA Glycosylase BKRF3 Contributes to Epstein-Barr Virus DNA Replication through Physical Interactions with Proteins in Viral DNA Replication Complex." Journal of Virology 88, no. 16: 8883-8899.

Journal article
Published: 19 February 2014 in Journal of Virology
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Epstein-Barr virus (EBV) lytic replication involves complex processes, including DNA synthesis, DNA cleavage and packaging, and virion egress. These processes require many different lytic gene products, but the mechanisms of their actions remain unclear, especially for DNA cleavage and packaging. According to sequence homology analysis, EBV BALF3, encoded by the third leftward open reading frame of the BamHI-A fragment in the viral genome, is a homologue of herpes simplex virus type 1 UL28. This gene product is believed to possess the properties of a terminase, such as nucleolytic activity on newly synthesized viral DNA and translocation of unit length viral genomes into procapsids. In order to characterize EBV BALF3, the protein was produced by and purified from recombinant baculoviruses and examined in an enzymatic reaction in vitro, which determined that EBV BALF3 acts as an endonuclease and its activity is modulated by Mg2+, Mn2+, and ATP. Moreover, in EBV-positive epithelial cells, BALF3 was expressed and transported from the cytoplasm into the nucleus following induction of the lytic cycle, and gene silencing of BALF3 caused a reduction of DNA packaging and virion release. Interestingly, suppression of BALF3 expression also decreased the efficiency of DNA synthesis. On the basis of these results, we suggest that EBV BALF3 is involved simultaneously in DNA synthesis and packaging and is required for the production of mature virions. IMPORTANCE Virus lytic replication is essential to produce infectious virions, which is responsible for virus survival and spread. This work shows that an uncharacterized gene product of the human herpesvirus Epstein-Barr virus (EBV), BALF3, is expressed during the lytic cycle. In addition, BALF3 mediates an endonucleolytic reaction and is involved in viral DNA synthesis and packaging, leading to influence on the production of mature virions. According to sequence homology and physical properties, the lytic gene product BALF3 is considered a terminase in EBV. These findings identify a novel viral gene with an important role in contributing to a better understanding of the EBV life cycle.

ACS Style

Shih-Hsin Chiu; Meng-Chuan Wu; Chung-Chun Wu; Yu-Ching Chen; Su-Fang Lin; John T.-A. Hsu; Chung-Shi Yang; Ching-Hwa Tsai; Kenzo Takada; Mei-Ru Chen; Jen-Yang Chen. Epstein-Barr Virus BALF3 Has Nuclease Activity and Mediates Mature Virion Production during the Lytic Cycle. Journal of Virology 2014, 88, 4962 -4975.

AMA Style

Shih-Hsin Chiu, Meng-Chuan Wu, Chung-Chun Wu, Yu-Ching Chen, Su-Fang Lin, John T.-A. Hsu, Chung-Shi Yang, Ching-Hwa Tsai, Kenzo Takada, Mei-Ru Chen, Jen-Yang Chen. Epstein-Barr Virus BALF3 Has Nuclease Activity and Mediates Mature Virion Production during the Lytic Cycle. Journal of Virology. 2014; 88 (9):4962-4975.

Chicago/Turabian Style

Shih-Hsin Chiu; Meng-Chuan Wu; Chung-Chun Wu; Yu-Ching Chen; Su-Fang Lin; John T.-A. Hsu; Chung-Shi Yang; Ching-Hwa Tsai; Kenzo Takada; Mei-Ru Chen; Jen-Yang Chen. 2014. "Epstein-Barr Virus BALF3 Has Nuclease Activity and Mediates Mature Virion Production during the Lytic Cycle." Journal of Virology 88, no. 9: 4962-4975.

Journal article
Published: 01 January 2014 in Applied Mechanics and Materials
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This paper presents a solution to calculate the traffic management and control facilities fault tolerance ability to driving mistakes due to drivers fault in perception, judgment and operation. Firstly, according to Shannon information theory, the information volume of eight types of contents on transportation management and control facilities are calculated. The total information volume of these eight types of contents is the basic driving fault tolerance of the facilities. Then, the right rate that facilities set and designed, driver conditions and transportation conditions are screened out for correction coefficients. Finally, the actual driving fault tolerance is given by the product of the basic driving fault tolerance and the three correction coefficients. The solution is useful to evaluate the intersection safety level.

ACS Style

Mei Ru Chen; Yu Long Pei; Li Wei Hu. A Model of the Driving Fault Tolerance of Traffic Management and Control Facilities at Urban Intersections. Applied Mechanics and Materials 2014, 496-500, 2751 -2755.

AMA Style

Mei Ru Chen, Yu Long Pei, Li Wei Hu. A Model of the Driving Fault Tolerance of Traffic Management and Control Facilities at Urban Intersections. Applied Mechanics and Materials. 2014; 496-500 ():2751-2755.

Chicago/Turabian Style

Mei Ru Chen; Yu Long Pei; Li Wei Hu. 2014. "A Model of the Driving Fault Tolerance of Traffic Management and Control Facilities at Urban Intersections." Applied Mechanics and Materials 496-500, no. : 2751-2755.

Journal article
Published: 15 August 2013 in Journal of Virology
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Epstein-Barr virus (EBV) alters the regulation and expression of a variety of cytokines in its host cells to modulate host immune surveillance and facilitate viral persistence. Using cytokine antibody arrays, we found that, in addition to the cytokines reported previously, two chemotactic cytokines, CCL3 and CCL4, were induced in EBV-infected B cells and were expressed at high levels in all EBV-immortalized lymphoblastoid cell lines (LCLs). Furthermore, EBV latent membrane protein 1 (LMP1)-mediated Jun N-terminal protein kinase activation was responsible for upregulation of CCL3 and CCL4. Inhibition of CCL3 and CCL4 in LCLs using a short hairpin RNA approach or by neutralizing antibodies suppressed cell proliferation and caused apoptosis, indicating that autocrine CCL3 and CCL4 are required for LCL survival and growth. Importantly, significant amounts of CCL3 were detected in EBV-positive plasma from immunocompromised patients, suggesting that EBV modulates this chemokine in vivo . This study reveals the regulatory mechanism and a novel function of CCL3 and CCL4 in EBV-infected B cells. CCL3 might be useful as a therapeutic target in EBV-associated lymphoproliferative diseases and malignancies.

ACS Style

Shu-Chun Tsai; Sue-Jane Lin; Cheau-Jye Lin; Ya-Ching Chou; Jiun-Han Lin; Te-Huei Yeh; Mei-Ru Chen; Li-Min Huang; Meng-You Lu; Ya-Chi Huang; Huan-Yun Chen; Ching-Hwa Tsai. Autocrine CCL3 and CCL4 Induced by the Oncoprotein LMP1 Promote Epstein-Barr Virus-Triggered B Cell Proliferation. Journal of Virology 2013, 87, 9041 -9052.

AMA Style

Shu-Chun Tsai, Sue-Jane Lin, Cheau-Jye Lin, Ya-Ching Chou, Jiun-Han Lin, Te-Huei Yeh, Mei-Ru Chen, Li-Min Huang, Meng-You Lu, Ya-Chi Huang, Huan-Yun Chen, Ching-Hwa Tsai. Autocrine CCL3 and CCL4 Induced by the Oncoprotein LMP1 Promote Epstein-Barr Virus-Triggered B Cell Proliferation. Journal of Virology. 2013; 87 (16):9041-9052.

Chicago/Turabian Style

Shu-Chun Tsai; Sue-Jane Lin; Cheau-Jye Lin; Ya-Ching Chou; Jiun-Han Lin; Te-Huei Yeh; Mei-Ru Chen; Li-Min Huang; Meng-You Lu; Ya-Chi Huang; Huan-Yun Chen; Ching-Hwa Tsai. 2013. "Autocrine CCL3 and CCL4 Induced by the Oncoprotein LMP1 Promote Epstein-Barr Virus-Triggered B Cell Proliferation." Journal of Virology 87, no. 16: 9041-9052.

Research article
Published: 17 May 2013 in Innate Immunity
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Upon virus infection, the host innate immune response is initiated through the activation of IFN regulatory factor 3 (IRF3) and NF-κB signaling pathways to induce IFN production. Previously, we demonstrated EBV BGLF4 kinase suppresses IRF3 function in a kinase activity-dependent manner. The replacement of Ser123, Ser173 and Thr180 into alanines at the proline-rich linker region of IRF3 abolishes BGLF4-mediated suppression. In this study, we show that BGLF4 phosphorylates glutathione-S-transferase (GST)–IRF3(110-202), but not GST–IRF3(110-202)3A mutant (S123/S173/T180A) in vitro. Compared with activation mimicking mutant IRF3(5D), the phosphorylation-defective IRF3(5D)3A shows a higher transactivation activity in reporter assays, whereas the phosphorylation-mimicking IRF3(5D)2D1E, with Ser123 and Ser173 mutated to aspartate and Thr180 to glutamate, has a much lower activity. To explore whether similar cellular regulation also exists in the absence of virus infection, candidate cellular kinases were predicted and the transactivation activity of IRF3 was examined with various kinase inhibitors. Glycogen synthase kinase 3 (GSK3) inhibitor LiCl specifically enhanced both IRF3(5D) and wild type IRF3 activity, even without stimulation. Expression of constitutive active GSK3β(S9A) represses LiCl-mediated enhancement of IRF3 transactivation activity. In vitro, both GSK3α and GSK3β phosphorylate IRF3 at the linker region. Collectively, data here suggest GSK3 phosphorylates IRF3 linker region in a way similar to viral kinase BGLF4.

ACS Style

Jiin-Tarng Wang; Ling-Shih Chang; Chun-Jen Chen; Shin-Lian Doong; Chou-Wei Chang; Mei-Ru Chen. Glycogen synthase kinase 3 negatively regulates IFN regulatory factor 3 transactivation through phosphorylation at its linker region. Innate Immunity 2013, 20, 78 -87.

AMA Style

Jiin-Tarng Wang, Ling-Shih Chang, Chun-Jen Chen, Shin-Lian Doong, Chou-Wei Chang, Mei-Ru Chen. Glycogen synthase kinase 3 negatively regulates IFN regulatory factor 3 transactivation through phosphorylation at its linker region. Innate Immunity. 2013; 20 (1):78-87.

Chicago/Turabian Style

Jiin-Tarng Wang; Ling-Shih Chang; Chun-Jen Chen; Shin-Lian Doong; Chou-Wei Chang; Mei-Ru Chen. 2013. "Glycogen synthase kinase 3 negatively regulates IFN regulatory factor 3 transactivation through phosphorylation at its linker region." Innate Immunity 20, no. 1: 78-87.

Journal article
Published: 30 November 2012 in The American Journal of Pathology
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Nasopharyngeal carcinoma (NPC) is characteristic for its strong association with Epstein-Barr virus (EBV) and high metastatic rate. Recently, overexpressed recepteur d'origine nantais (RON) (MST1R), receptor tyrosine kinase has been reported in human cancers and tumor metastasis. Therefore, the role of RON in EBV-associated NPC and its metastasis was investigated. Here we show that RON was found in NPC but not in control tissues. A significant correlation of latent membrane protein 1 (LMP1) and RON expression was found in NPC (Pearson's χ2 test; P = 0.0023). At the molecular level, LMP1 stimulates nuclear factor-κB binding to the RON promoter through its carboxyl-terminal activation region 1 to induce expression of RON. Knockdown of RON in cells expressing LMP1 significantly reverses LMP1-induced epithelial-mesenchymal transition and suppresses LMP1-induced cell migration and invasion. These results suggest an important role of RON in the tumorigenesis and metastasis of NPC and RON may be a novel therapeutic target for EBV-associated NPC.

ACS Style

Ya-Ching Chou; Chi-Long Chen; Te-Huei Yeh; Sue-Jane Lin; Mei-Ru Chen; Shin-Lian Doong; Jean Lu; Ching-Hwa Tsai. Involvement of Recepteur d'Origine Nantais Receptor Tyrosine Kinase in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma and Its Metastasis. The American Journal of Pathology 2012, 181, 1773 -1781.

AMA Style

Ya-Ching Chou, Chi-Long Chen, Te-Huei Yeh, Sue-Jane Lin, Mei-Ru Chen, Shin-Lian Doong, Jean Lu, Ching-Hwa Tsai. Involvement of Recepteur d'Origine Nantais Receptor Tyrosine Kinase in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma and Its Metastasis. The American Journal of Pathology. 2012; 181 (5):1773-1781.

Chicago/Turabian Style

Ya-Ching Chou; Chi-Long Chen; Te-Huei Yeh; Sue-Jane Lin; Mei-Ru Chen; Shin-Lian Doong; Jean Lu; Ching-Hwa Tsai. 2012. "Involvement of Recepteur d'Origine Nantais Receptor Tyrosine Kinase in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma and Its Metastasis." The American Journal of Pathology 181, no. 5: 1773-1781.

Journal article
Published: 21 November 2012 in Journal of Virology
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Nuclear export is an important process that not only regulates the functions of cellular factors but also facilitates the assembly of viral nucleoprotein complexes. Chromosome region maintenance 1 (CRM1) that mediates the transport of proteins bearing the classical leucine-rich nuclear export signal (NES) is the best-characterized nuclear export receptor. Recently, several CRM1-independent nuclear export pathways were also identified. The nuclear export of the large form of hepatitis delta antigen (HDAg-L), a nucleocapsid protein of hepatitis delta virus (HDV), which contains a CRM1-independent proline-rich NES, is mediated by the host NES-interacting protein (NESI). The mechanism of the NESI protein in mediating nuclear export is still unknown. In this study, NESI was characterized as a highly glycosylated membrane protein. It interacted and colocalized well in the nuclear envelope with lamin A/C and nucleoporins. Importantly, HDAg-L could be coimmunoprecipitated with lamin A/C and nucleoporins. In addition, binding of the cargo HDAg-L to the C terminus of NESI was detected for the wild-type protein but not for the nuclear export-defective HDAg-L carrying a P205A mutation [HDAg-L(P205A)]. Knockdown of lamin A/C effectively reduced the nuclear export of HDAg-L and the assembly of HDV. These data indicate that by forming complexes with lamin A/C and nucleoporins, NESI facilitates the CRM1-independent nuclear export of HDAg-L.

ACS Style

Cheng Huang; Jia-Yin Jiang; Shin C. Chang; Yeou-Guang Tsay; Mei-Ru Chen; Ming-Fu Chang. Nuclear Export Signal-Interacting Protein Forms Complexes with Lamin A/C-Nups To Mediate the CRM1-Independent Nuclear Export of Large Hepatitis Delta Antigen. Journal of Virology 2012, 87, 1596 -1604.

AMA Style

Cheng Huang, Jia-Yin Jiang, Shin C. Chang, Yeou-Guang Tsay, Mei-Ru Chen, Ming-Fu Chang. Nuclear Export Signal-Interacting Protein Forms Complexes with Lamin A/C-Nups To Mediate the CRM1-Independent Nuclear Export of Large Hepatitis Delta Antigen. Journal of Virology. 2012; 87 (3):1596-1604.

Chicago/Turabian Style

Cheng Huang; Jia-Yin Jiang; Shin C. Chang; Yeou-Guang Tsay; Mei-Ru Chen; Ming-Fu Chang. 2012. "Nuclear Export Signal-Interacting Protein Forms Complexes with Lamin A/C-Nups To Mediate the CRM1-Independent Nuclear Export of Large Hepatitis Delta Antigen." Journal of Virology 87, no. 3: 1596-1604.