scholarly journals Levels of p53 in Epstein–Barr Virus-Infected Cells Determine Cell Fate: Apoptosis, Cell Cycle Arrest at the G1/S Boundary without Apoptosis, Cell Cycle Arrest at the G2/M Boundary without Apoptosis, or Unrestricted Proliferation

Virology ◽  
1998 ◽  
Vol 251 (2) ◽  
pp. 217-226 ◽  
Author(s):  
Weiping Chen ◽  
Shuang Huang ◽  
Neil R. Cooper
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Fate ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Cycle Arrest ◽  
Infected Cells ◽  
Epstein Barr

scholarly journals Radiosensitization Effect of Nedaplatin on Nasopharyngeal Carcinoma Cells in Different Status of Epstein-Barr Virus Infection

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Li Yin ◽  
Jing Wu ◽  
Jianfeng Wu ◽  
Jinjun Ye ◽  
Xuesong Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nasopharyngeal Carcinoma ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Cycle Arrest ◽  
M Phase ◽  
Epstein Barr ◽  
Mts Assay

This study aims to evaluate the radiosensitization effect of nedaplatin on nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV) status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were treated with 0–100 μg/mL nedaplatin, and inhibitory effects on cell viability and IC50were calculated by MTS assay. We assessed changes in radiosensitivity of cells by MTS and colony formation assays, and detected the apoptosis index and changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50values of 34.32 and 63.69 μg/mL, respectively. Compared with radiation alone, nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin radiosensitized human NPC cells CNE-2 and C666, with a significantly greater effect on the former. The mechanisms of radiosensitization include induction of apoptosis and enhancement of cell cycle arrest in G2/M phase.

scholarly journals Epstein–Barr virus Rta-mediated transactivation of p21 and 14-3-3σ arrests cells at the G1/S transition by reducing cyclin E/CDK2 activity

2012 ◽  
Vol 93 (1) ◽  
pp. 139-149 ◽  
Author(s):  
Sheng-Yen Huang ◽  
Min-Jie Hsieh ◽  
Chu-Ying Chen ◽  
Yen-Ju Chen ◽  
Jen-Yang Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Epstein Barr Virus ◽  
Cyclin E ◽  
Lytic Replication ◽  
Immediate Early ◽  
Luciferase Reporter ◽  
Barr Virus ◽  
Cycle Arrest ◽  
Epstein Barr

Many herpesviral immediate-early proteins promote their robust lytic phase replications by hijacking the cell cycle machinery. Previously, lytic replication of Epstein–Barr virus (EBV) was found to be concurrent with host cell cycle arrest. In this study, we showed that ectopic expression of EBV immediate-early protein Rta in HEp-2 cells resulted in increased G1/S population, hypophosphorylation of pRb and decreased incorporation of 5-bromo-2′-deoxyuridine. In addition, EBV Rta transcriptionally upregulates the expressions of p21 and 14-3-3σ in HEp-2 cells, 293 cells and nasopharyngeal carcinoma TW01 cells. Although p21 and 14-3-3σ are known targets for p53, Rta-mediated p21 and 14-3-3σ transactivation can be detected in the absence of p53. In addition, results from luciferase reporter assays indicated that direct binding of Rta to either promoter sequences is not required for activation. On the other hand, a special class of Sp1-responsive elements was involved in Rta-mediated transcriptional activation on both promoters. Finally, Rta-induced p21 expression diminished the activity of CDK2/cyclin E complex, and, Rta-induced 14-3-3σ expression sequestered CDK1 and CDK2 in the cytoplasm. Based on these results, we hypothesize that through the disruption of CDK1 and CDK2 activities, EBV Rta might contribute to cell cycle arrest in EBV-infected epithelial cells during viral reactivation.

scholarly journals CCAAT/Enhancer Binding Protein α Interacts with ZTA and Mediates ZTA-Induced p21CIP-1 Accumulation and G1 Cell Cycle Arrest during the Epstein-Barr Virus Lytic Cycle

2003 ◽  
Vol 77 (2) ◽  
pp. 1481-1500 ◽  
Author(s):  
Frederick Y. Wu ◽  
Honglin Chen ◽  
Shizhen Emily Wang ◽  
Collette M. J. apRhys ◽  
Gangling Liao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Epstein Barr Virus ◽  
Adenovirus Vector ◽  
Lytic Cycle ◽  
Barr Virus ◽  
Cycle Arrest ◽  
Enhancer Binding Protein ◽  
Epstein Barr ◽  
P21 Promoter

ABSTRACT Cellular CCAAT/enhancer binding protein α (C/EBPα) promotes cellular differentiation and has antimitotic activities involving cell cycle arrest at G1/S through stabilization of p21CIP-1/WAF1 and through transcriptional activation of the p21 promoter. The Epstein-Barr virus lytic-cycle transactivator protein ZTA is known to arrest the host cell cycle at G1/S via a p53-independent p21 pathway, but the detailed molecular mechanisms involved have not been defined. To further evaluate the role of ZTA in cell cycle arrest, we constructed a recombinant adenovirus vector expressing ZTA (Ad-ZTA), whose level of expression at a low multiplicity of infection in normal human diploid fibroblast (HF) cells was lower than or equal to the physiological level seen in Akata cells lytically induced by EBV (EBV-Akata cells). Fluorescence-activated cell sorting analysis of HF cells infected with Ad-ZTA confirmed that G1/S cell cycle arrest occurred in the majority of ZTA-positive cells, but not with an adenovirus vector expressing green fluorescent protein. Double-label immunofluorescence assays (IFA) performed with Ad-ZTA-infected HF cells revealed that only ZTA-positive cells induced the expression of both endogenous C/EBPα and p21 and blocked the progression into S phase, as detected by a lack of incorporation of bromodeoxyuridine. The stimulation of endogenous ZTA protein expression either through treatment with tetradecanoyl phorbol acetate in D98/HR1 cells or through B-cell receptor cross-linking with anti-immunoglobulin G antibody in EBV-Akata cells also coincided with the induction of both C/EBPα and p21 and their mRNAs, as assayed by Northern blot, Western blot, and IFA experiments. Mechanistically, the ZTA protein proved to directly interact with C/EBPα by coimmunoprecipitation in EBV-Akata cells and with DNA-bound C/EBPα in electrophoretic mobility shift assay experiments, and the in vitro interaction domain encompassed the basic leucine zipper domain of ZTA. ZTA also specifically protected C/EBPα from degradation in a protein stability assay with a non-EBV-induced Akata cell proteasome extract. Furthermore, both C/EBPα and ZTA were found to specifically associate with the C/EBPα promoter in chromatin immunoprecipitation assays, but the interaction with ZTA appeared to be mediated by C/EBPα because it was abolished by clearing with anti-C/EBPα antibody. ZTA did not bind to or activate the C/EBPα promoter directly but cooperatively enhanced the positive autoregulation of the C/EBPα promoter by cotransfected C/EBPα in transient luciferase reporter gene assays with Vero and HeLa cells as well as with DG75 B lymphocytes. Similarly, ZTA alone had little effect on the p21 promoter in transient reporter gene assays, but in the presence of cotransfected C/EBPα, ZTA enhanced the level of C/EBPα activation. This effect proved to require a previously unrecognized region in the proximal p21 promoter that contains three high-affinity C/EBPα binding sites. Finally, in C/EBPα-deficient mouse embryonic fibroblasts (MEF), Ad-ZTA was unable to induce either p21 or G1 arrest, whereas it was able to induce both in wild-type MEF. Overall, we conclude that C/EBPα is essential for at least one pathway of ZTA-induced G1 arrest during EBV lytic-cycle DNA replication and that this process involves a physical piggyback interaction between ZTA and C/EBPα leading to greatly enhanced C/EBPα and p21 levels through both transcriptional and posttranslational mechanisms.

scholarly journals Cell cycle arrest induced by engagement of B7-H4 on Epstein-Barr virus-positive B-cell lymphoma cell lines

Immunology ◽  
2009 ◽  
Vol 128 (3) ◽  
pp. 360-368 ◽  
Author(s):  
Ga Bin Park ◽  
Hyunkeun Song ◽  
Yeong-Seok Kim ◽  
Minjung Sung ◽  
Jeoung W. Ryu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cell ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Barr Virus ◽  
Cycle Arrest ◽  
Epstein Barr

scholarly journals Cell Cycle Regulation by Kaposi's Sarcoma-Associated Herpesvirus K-bZIP: Direct Interaction with Cyclin-CDK2 and Induction of G1 Growth Arrest

2003 ◽  
Vol 77 (17) ◽  
pp. 9652-9661 ◽  
Author(s):  
Yoshihiro Izumiya ◽  
Su-Fang Lin ◽  
Thomas J. Ellison ◽  
Alon M. Levy ◽  
Greg L. Mayeur ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Kaposi's Sarcoma ◽  
Epstein Barr Virus ◽  
Kaposi’S Sarcoma ◽  
Barr Virus ◽  
Infected Cells ◽  
Epstein Barr ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
Cycle Regulation

ABSTRACT In order to cope with hostile host environments, many viruses have developed strategies to perturb the cellular machinery to suit their replication needs. Some herpesvirus genes protect cells from undergoing apoptosis to prolong the lives of infected cells, while others, such as Epstein-Barr virus Zta, slow down the G1/S transition phase to allow ample opportunity for transcription and translation of viral genes before the onset of cellular genomic replication. In this study, we investigated whether Kaposi's sarcoma-associated herpesvirus (KSHV) K-bZIP, a homologue of the Epstein-Barr virus transcription factor BZLF1 (Zta), plays a role in cell cycle regulation. Here we show that K-bZIP physically associates with cyclin-CDK2 and downmodulates its kinase activity. The association can be detected in the natural environment of KSHV-infected cells without artificial overexpression of either component. With purified protein, it can be shown that the interaction between K-bZIP and cyclin-CDK2 is direct and that K-bZIP alone is sufficient to inhibit CDK2 activity. The interacting domain of K-bZIP has been mapped to the basic region. The result of these associations is a prolonged G1 phase, accompanied by the induction of p21 and p27 in a naturally infected B-cell line. Thus, in addition to the previously described transcription and genome replication functions, a new role of K-bZIP in KSHV replication is identified in this report.

scholarly journals Tofacitinib induces G1 cell-cycle arrest and inhibits tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells

Oncotarget ◽  
2016 ◽  
Vol 7 (47) ◽  
pp. 76793-76805 ◽  
Author(s):  
Shotaro Ando ◽  
Jun-ichi Kawada ◽  
Takahiro Watanabe ◽  
Michio Suzuki ◽  
Yoshitaka Sato ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Natural Killer Cell ◽  
Tumor Growth ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
Killer Cell ◽  
Barr Virus ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Epstein Barr

scholarly journals The Epstein-Barr Virus Protein BRLF1 Activates S Phase Entry through E2F1 Induction

1999 ◽  
Vol 73 (8) ◽  
pp. 6540-6550 ◽  
Author(s):  
Jennifer J. Swenson ◽  
Amy E. Mauser ◽  
William K. Kaufmann ◽  
Shannon C. Kenney
Keyword(s):  
Cell Cycle ◽  
Epstein Barr Virus ◽  
Human Fibroblasts ◽  
S Phase ◽  
Lytic Replication ◽  
Osteosarcoma Cell ◽  
Barr Virus ◽  
Infected Cells ◽  
Epstein Barr ◽  
Phase Entry

ABSTRACT The Epstein-Barr Virus (EBV) immediate-early protein BRLF1 is one of two transactivators which mediate the switch from latent to lytic replication in EBV-infected cells. DNA viruses often modulate the function of critical cell cycle proteins to maximize the efficiency of virus replication. Here we have examined the effect of BRLF1 on cell cycle progression. A replication-deficient adenovirus expressing BRLF1 (AdBRLF1) was used to infect normal human fibroblasts and various epithelial cell lines. BRLF1 expression induced S phase entry in contact-inhibited fibroblasts and in the human osteosarcoma cell line U-2 OS. AdBRLF1 infection produced a dramatic increase in the level of E2F1 but not E2F4. In contrast, the levels of Rb, p107, and p130 were decreased in AdBRLF1-infected cells. Electrophoretic mobility shift assays confirmed an increased level of free E2F1 in the AdBRLF1-infected human fibroblasts. Consistent with the previously described effect of E2F1, AdBRLF1-infected fibroblasts had increased levels of p53 and p21 and died by apoptosis. BRLF1-induced activation of E2F1 may be required for efficient EBV lytic replication, since at least one critical viral replication gene (the viral DNA polymerase) is activated by E2F (C. Liu, N. D. Sista, and J. S. Pagano, J. Virol. 70:2545–2555, 1996).

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