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An investigation into the effects of the Epstein-Barr virus-encoded nuclear protein, EBNA1, on the TGFβ and BMP signaling pathways in human epithelial cells

Date, Kathryn Louise (2012)
Ph.D. thesis, University of Birmingham.

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Abstract

In addition to its essential roles in the maintenance, replication and transcription of the EBV genome, EBNA1 has more recently been shown to influence the transcription of cellular genes and to modulate the activity of key cellular signalling pathways. EBNA1 has previously been shown to abrogate TGFβ signalling in carcinoma cell lines, although the exact mechanism remains to be elucidated. This study has endeavoured to further dissect this observation, whilst revealing a novel function for EBNA1 in the activation of the closely-related BMP signalling pathway. The observed abrogation of canonical TGFβ signalling is now proposed to be the result of an EBNA1-mediated induction of negative regulators, while a concomitant increase in secreted TGFβ, in combination with a shift towards linker region phosphorylation of the R-Smad proteins in EBNA1-expressing cells conceivably constitutes a method of promoting pro-tumourigenic TGFβ-mediated effects, such as cellular migration. In addition, results demonstrating the activation of BMP signalling upon the expression of EBNA1, and in EBV-positive cell lines, are also indicative of a role in the promotion of migration, and potentially metastasis. In this way, EBNA1 may mediate effects that contribute to the development of EBV-associated tumours.

Type of Work:Ph.D. thesis.
Supervisor(s):Dawson, Christopher and ONeill, John
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Cancer Studies
Subjects:RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Institution:University of Birmingham
ID Code:3223
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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