Search

Your search keyword '"Arrand, John R."' showing total 157 results
Start Over Author "Arrand, John R."
157 results on '"Arrand, John R."'

16. Epstein-Barr virus-encoded EBNA1 enhances RNA polymerase III-dependent EBER expression through induction of EBER-associated cellular transcription factors

Author

Owen Thomas J, O'Neil John D, Dawson Christopher W, Hu Chunfang, Chen Xiaoyi, Yao Yunhong, Wood Victoria HJ, Mitchell Louise E, White Robert J, Young Lawrence S, and Arrand John R

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Epstein-Barr Virus (EBV)-encoded RNAs (EBERs) are non-polyadenylated RNA molecules transcribed from the EBV genome by RNA polymerase III (pol III). EBERs are the most abundant viral latent gene products, although the precise mechanisms by which EBV is able to achieve such high levels of EBER expression are not fully understood. Previously EBV has been demonstrated to induce transcription factors associated with EBER expression, including pol III transcription factors and ATF-2. We have recently demonstrated that EBV-encoded nuclear antigen-1 (EBNA1) induces cellular transcription factors, and given these findings, we investigated the role of EBNA1 in induction of EBER-associated transcription factors. Results Our data confirm that in epithelial cells EBNA1 can enhance cellular pol III transcription. Transient expression of EBNA1 in Ad/AH cells stably expressing the EBERs led to induction of both EBER1 and EBER2 and conversely, expression of a dominant negative EBNA1 led to reduced EBER expression in EBV-infected Ad/AH cells. EBNA1 can induce transcription factors used by EBER genes, including TFIIIC, ATF-2 and c-Myc. A variant chromatin precipitation procedure showed that EBNA1 is associated with the promoters of these genes but not with the promoters of pol III-transcribed genes, including the EBERs themselves. Using shRNA knock-down, we confirm the significance of both ATF-2 and c-Myc in EBER expression. Further, functional induction of a c-Myc fusion protein led to increased EBER expression, providing c-Myc binding sites upstream of EBER1 were intact. In vivo studies confirm elevated levels of the 102 kD subunit of TFIIIC in the tumour cells of EBV-positive nasopharyngeal carcinoma biopsies. Conclusions Our findings reveal that EBNA1 is able to enhance EBER expression through induction of cellular transcription factors and add to the repertoire of EBNA1's transcription-regulatory properties.

Published
2010
Full Text
View/download PDF

18. Epstein-Barr virus-encoded EBNA1 inhibits the canonical NF-κB pathway in carcinoma cells by inhibiting IKK phosphorylation

Author

Maia Sonia P, Date Kathryn L, Owen Thomas J, Shah Khilan M, Hu Chunfang, Dawson Christopher W, Valentine Robert, Shao Jianyong, Arrand John R, Young Lawrence S, and O'Neil John D

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The Epstein-Barr virus (EBV)-encoded EBNA1 protein is expressed in all EBV-associated tumours, including undifferentiated nasopharyngeal carcinoma (NPC), where it is indispensable for viral replication, genome maintenance and viral gene expression. EBNA1's transcription factor-like functions also extend to influencing the expression of cellular genes involved in pathways commonly dysregulated during oncogenesis, including elevation of AP-1 activity in NPC cell lines resulting in enhancement of angiogenesis in vitro. In this study we sought to extend these observations by examining the role of EBNA1 upon another pathway commonly deregulated during carcinogenesis; namely NF-κB. Results In this report we demonstrate that EBNA1 inhibits the canonical NF-κB pathway in carcinoma lines by inhibiting the phosphorylation of IKKα/β. In agreement with this observation we find a reduction in the phosphorylation of IκBα and reduced phosphorylation and nuclear translocation of p65, resulting in a reduction in the amount of p65 in nuclear NF-κB complexes. Similar effects were also found in carcinoma lines infected with recombinant EBV and in the EBV-positive NPC-derived cell line C666-1. Inhibition of NF-κB was dependent upon regions of EBNA1 essential for gene transactivation whilst the interaction with the deubiquitinating enzyme, USP7, was entirely dispensable. Furthermore, in agreement with EBNA1 inhibiting p65 NF-κB we demonstrate that p65 was exclusively cytoplasmic in 11 out of 11 NPC tumours studied. Conclusions Inhibition of p65 NF-κB in murine and human epidermis results in tissue hyperplasia and the development of squamous cell carcinoma. In line with this, p65 knockout fibroblasts have a transformed phenotype. Inhibition of p65 NF-κB by EBNA1 may therefore contribute to the development of NPC by inducing tissue hyperplasia. Furthermore, inhibition of NF-κB is employed by viruses as an immune evasion strategy which is also closely linked to oncogenesis during persistent viral infection. Our findings therefore further implicate EBNA1 in playing an important role in the pathogenesis of NPC.

Published
2010
Full Text
View/download PDF

26. Genome Diversity of Epstein-Barr Virus from Multiple Tumor Types and Normal Infection

Author

Palser, Anne L., primary, Grayson, Nicholas E., additional, White, Robert E., additional, Corton, Craig, additional, Correia, Samantha, additional, Ba abdullah, Mohammed M., additional, Watson, Simon J., additional, Cotten, Matthew, additional, Arrand, John R., additional, Murray, Paul G., additional, Allday, Martin J., additional, Rickinson, Alan B., additional, Young, Lawrence S., additional, Farrell, Paul J., additional, and Kellam, Paul, additional

Published
2015
Full Text
View/download PDF

29. A Global View of the Oncogenic Landscape in Nasopharyngeal Carcinoma: An Integrated Analysis at the Genetic and Expression Levels

Author

Hu, Chunfang, primary, Wei, Wenbin, additional, Chen, Xiaoyi, additional, Woodman, Ciaran B., additional, Yao, Yunhong, additional, Nicholls, John M., additional, Joab, Irène, additional, Sihota, Sim K., additional, Shao, Jian-Yong, additional, Derkaoui, K. Dalia, additional, Amari, Aicha, additional, Maloney, Stephanie L., additional, Bell, Andrew I., additional, Murray, Paul G., additional, Dawson, Christopher W., additional, Young, Lawrence S., additional, and Arrand, John R., additional

Published
2012
Full Text
View/download PDF

37. Comparative analysis of the expression of the epstein‐barr virus (EBV) anti‐apoptotic gene BHRF1 in nasopharyngeal carcinoma and EBV‐related lymphoid diseases

Author

Nicholls, John, primary, Kremmer, Elisabeth, additional, Meseda, Clement A., additional, Mackett, Mike, additional, Hahn, Peter, additional, Gulley, Margaret L., additional, Brink, Antoinette, additional, Swinnen, Lode J., additional, Greenspan, John, additional, De Souza, Yvonne, additional, Grässer, Friedrich, additional, Sham, Jonathan, additional, Ng, Mun‐Hon, additional, and Arrand, John R., additional

Published
2001
Full Text
View/download PDF

47. Reply

Author

Stewart, James P., primary and Arrand, John R., additional

Published
1994
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results