scholarly journals Epstein-Barr virus oncoprotein LMP1 mediates survivin upregulation by p53 contributing to G1/S cell cycle progression in nasopharyngeal carcinoma

2012 ◽  
Vol 29 (4) ◽  
pp. 574-580 ◽  
Author(s):  
LILI GUO ◽  
MIN TANG ◽  
LIFANG YANG ◽  
LANBO XIAO ◽  
ANN M. BODE ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Micro RNAs of Epstein-Barr Virus Promote Cell Cycle Progression and Prevent Apoptosis of Primary Human B Cells

2010 ◽  
Vol 6 (8) ◽  
pp. e1001063 ◽  
Author(s):  
Eri Seto ◽  
Andreas Moosmann ◽  
Sebastian Grömminger ◽  
Nicole Walz ◽  
Adam Grundhoff ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
Epstein Barr Virus ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Barr Virus ◽  
Human B Cells ◽  
Micro Rnas ◽  
Promote Cell Cycle Progression ◽  
Epstein Barr

scholarly journals Epstein-Barr Virus Nuclear Antigen 3C Facilitates Cell Proliferation by Regulating Cyclin D2

2018 ◽  
Vol 92 (18) ◽  
Author(s):  
Yonggang Pei ◽  
Rajnish Kumar Singh ◽  
Sanket Kumar Shukla ◽  
Fengchao Lang ◽  
Shengwei Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Epstein Barr Virus ◽  
Cell Cycle Progression ◽  
Nuclear Antigen ◽  
Cyclin D2 ◽  
Cycle Progression ◽  
Barr Virus ◽  
Epstein Barr ◽  
Related Proteins

ABSTRACTCell cycle regulation is one of the hallmarks of virus-mediated oncogenesis. Epstein-Barr virus (EBV)-induced lymphomas express a repertoire of essential viral latent proteins that regulate expression of cell cycle-related proteins to dysregulate this process, thereby facilitating the proliferation of infected cells. We now demonstrate that the essential EBV latent protein 3C (EBNA3C) stabilizes cyclin D2 to regulate cell cycle progression. More specifically, EBNA3C directly binds to cyclin D2 and they colocalize together in nuclear compartments. We show that EBNA3C regulates the promoter of cyclin D2 through cooperation with master transcription factor Bcl6 and enhances its stability by inhibiting its ubiquitin-dependent degradation. EBNA3C also promoted cell proliferation in the presence of cyclin D2, suggesting that cyclin D2 contributes to EBNA3C-mediated cell cycle progression. These results provide new clues as to the role of this essential viral latent protein and its ability to regulate expression of cellular factors, which drives the oncogenic process.IMPORTANCEEpstein-Barr virus (EBV) is the first identified human tumor virus and is associated with a range of human cancers. During EBV-induced lymphomas, the essential viral latent proteins modify the expression of cell cycle-related proteins to disturb the cell cycle process, thereby facilitating the proliferative process. The essential EBV nuclear antigen 3C (EBNA3C) plays an important role in EBV-mediated B-cell transformation. Here we show that EBNA3C stabilizes cyclin D2 to regulate cell cycle progression. More specifically, EBNA3C directly binds to cyclin D2, and they colocalize together in nuclear compartments. EBNA3C enhances cyclin D2 stability by inhibiting its ubiquitin-dependent degradation and significantly promotes cell proliferation in the presence of cyclin D2. Our results provide novel insights into the function of EBNA3C on cell progression by regulating the cyclin D2 protein and raise the possibility of the development of new anticancer therapies against EBV-associated cancers.

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 Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Yueshuo Li ◽  
Feng Shi ◽  
Jianmin Hu ◽  
Longlong Xie ◽  
Lin Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Viral Replication ◽  
Cell Cycle Progression ◽  
Negative Regulator ◽  
Protein Loss ◽  
Cycle Progression ◽  
Barr Virus ◽  
Cycle Arrest ◽  
Epstein Barr

Abstractp18 is a key negative regulator of cell cycle progression and mediates cell cycle arrest at the G1/S phase. Ubiquitination is the prime mechanism in regulating p18 protein abundance. However, so far no post- translational regulator, especially DUBs, has been identified to regulate the protein stability of p18. In this paper, we identified CYLD as a deubiquitinase of p18, which binds to and removes the K48-linked polyubiquitylation chains conjugated onto p18, thus stabilizing the p18 protein. Loss of CYLD causes the degradation of p18 and induces the G1/S transition. Epstein–Barr virus (EBV), is the human oncovirus etiologically linked to nasopharyngeal carcinoma (NPC). Here we found that EBV drives a replication passive environment by deregulating the CYLD-p18 axis. Functionally, CYLD inhibits cell proliferation and tumorigenesis through p18 in vivo. Restoring CYLD prevents EBV induced viral replication and tumor growth. Collectively, our results identify CYLD directly stabilizes p18 to regulate the cellular G1/S transition. The reconstitution of CYLD-p18 axis could be a promising approach for EBV-positive cancer therapy.

scholarly journals Epstein-Barr Virus Nuclear Antigen 3C Regulates Cyclin A/p27 Complexes and Enhances Cyclin A-Dependent Kinase Activity

2004 ◽  
Vol 78 (4) ◽  
pp. 1981-1991 ◽  
Author(s):  
Jason S. Knight ◽  
Erle S. Robertson
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Cell Transformation ◽  
Cyclin A ◽  
Nuclear Antigen ◽  
Cycle Progression ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is essential for primary B-cell transformation. In this report we show that cyclin A, an activator of S phase progression, bound tightly to EBNA3C. EBNA3C interacted with cyclin A in vitro and associated with cyclin A complexes in EBV-transformed lymphoblastoid cell lines. Importantly, EBNA3C stimulated cyclin A-dependent kinase activity and rescued p27-mediated inhibition of cyclin A/Cdk2 kinase activity by decreasing the molecular association between cyclin A and p27 in cells. Additionally, phosphorylation of the retinoblastoma protein, a major regulator of cell cycle progression, was enhanced both in vitro and in vivo in the presence of EBNA3C. Cyclin A interacted with a region of the carboxy terminus of EBNA3C, shown to be important both for stimulation of cyclin A-dependent kinase activity and for cell cycle progression. This provides the first evidence of an essential EBV latent antigen's directly targeting a cell cycle regulatory protein and suggests a novel mechanism by which EBV deregulates the mammalian cell cycle, which is of critical importance in B-cell transformation.

scholarly journals p16INK4A-independence of Epstein–Barr virus-induced cell proliferation and virus latency

2004 ◽  
Vol 85 (6) ◽  
pp. 1381-1386 ◽  
Author(s):  
Michelle J. Hayes ◽  
Anna Koundouris ◽  
Nelleke Gruis ◽  
Wilma Bergman ◽  
Gordon G. Peters ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Epstein Barr Virus ◽  
Cell Cycle Progression ◽  
Restriction Point ◽  
Barr Virus ◽  
Virus Latency ◽  
Cycle Arrest ◽  
Direct Binding ◽  
Promote Cell Cycle Progression ◽  
Epstein Barr

Epstein–Barr virus (EBV) has the ability to promote cell cycle progression following the initial infection of primary resting B-lymphocytes and to cause cell cycle arrest at the onset of the viral replicative cycle. Various mechanisms have been proposed for the proliferative effects, including the up-regulation of cyclin D2 by the viral EBNA-2 and EBNA-LP proteins, direct binding of EBNA3C to the retinoblastoma protein (pRb), and down-regulation of the p16INK4A tumour suppressor by the viral LMP1 product. To try to gain insight into the relative importance of these mechanisms, the ability of EBV to immortalize lymphocytes from an individual who is genetically deficient for p16INK4A was examined. From detailed analyses of the resultant lymphoblastoid cell lines it is concluded that p16INK4A status has little bearing on EBV's ability to manipulate the cell cycle machinery and a model to accommodate the previously proposed routes taken by EBV to bypass the restriction point is presented.

Downregulation of Epstein-barr Virus-Encoded Latent Membrane Protein-1 by Arsenic Trioxide in Nasopharyngeal Carcinoma Cells

2006 ◽  
Vol 92 (2) ◽  
pp. 140-148 ◽  
Author(s):  
Caiwen Du ◽  
Bogui Wen ◽  
Derui Li ◽  
Yingcheng Lin ◽  
Yuwu Zheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nasopharyngeal Carcinoma ◽  
Arsenic Trioxide ◽  
Epstein Barr Virus ◽  
Mrna Level ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 1 ◽  
Cell Cycle Distribution ◽  
Barr Virus ◽  
Epstein Barr

Aims and Background It was documented that nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) and that EBV-encoded latent membrane protein-1 expression (LMP1) plays an important role in the pathogenesis of NPC. In preclinical studies, arsenic trioxide (As2O3) has been identified as a promising anticancer agent for treatment of NPC. The purpose of this study is to investigate if this agent can inhibit the expression of LMP1 and therefore lead to growth inhibition of NPC cells in vitro. Methods LMP1-positive NPC cells, HNE1-LMP1, were treated with 3 umol/L of As2O3 for 96 hours. The LMP1 protein expression and mRNA level in HNE1-LMP1 cells were determined by western blot, confocal immunofluorescence staining and semiquantitative reverse transcriptase reaction (RT-PCR). Apoptosis was determined by light microscopy and the TUNEL method. Alterations in the cell cycle distribution were also investigated by flow cytometry. MTT assay and colony formation assay were used to detect the proliferation of the cells. The LMP1-negative parental cell lines HNE1 and HNE2 were used as control in an attempt to elucidate the role of LMP1 in the anticancer effect of As2O3 on NPC cells. Results The expression of LMP1 at the protein and mRNA level was reduced after exposure to 3 umol/L As2O3. This dose of As2O3 significantly induced apoptosis and growth retardation of HNE1-LMP1 cells. In addition, more HNE1-LMP1 cells were induced to G0/G1 and G2/M arrest. The same dose of As2O3 had a moderate effect on HNE1 and HNE2 cells. Conclusion Arsenic trioxide can inhibit LMP1 expression and dictate apoptosis and alterations of cell cycle distribution as well as growth retardation. LMP1-positive NPC cells are more sensitive to As2O3 treatment than LMP1-negative NPC cells.

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