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Regulation of apoptosis and desmosomes by RhoE

Ryan, Katie Rose (2010)
Ph.D. thesis, University of Birmingham.

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The human epidermis is a self-renewing stratified epithelial tissue that forms the outermost protective layer of the skin. The epidermis is comprised of a number of cell types, the most abundant of which are keratinocytes. Normal function of the epidermis requires that keratinocyte proliferation, differentiation, and apoptosis be precisely regulated and a failure to regulate these processes is a feature of many skin diseases. Although the precise mechanism by which epidermal homeostasis is regulated is still far from clear, much progress has been made in the characterisation of signaling pathways involved in normal epidermal function. A key group of signaling proteins that have been clearly implicated in epidermal function are the Rho family of small GTP-binding proteins. This thesis focuses on one member of the family, RhoE/Rnd3, and the analysis of the role it plays in the regulation of proliferation, differentiation, apoptosis and cell-cell adhesion in the epidermis. Use of RNA interference to specifically ‘knock-down’ expression of RhoE has led to the discovery of a novel role for RhoE in regulation of cell-cell adhesion and apoptosis. Loss of RhoE expression resulted in keratinocytes developing resistance to apoptosis mediated via either the intrinsic or extrinsic pathways. RhoE depletion was also associated with increased expression of desmosomal proteins and increased numbers of desmosomes. Resistance to apoptosis was shown to be a function of desmosome-mediated cell-cell adhesion and a component of demosomes – plakoglobin – was shown to play a key role in RhoE-mediated resistance to apoptosis.

Type of Work:Ph.D. thesis.
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:RL Dermatology
QH301 Biology
Institution:University of Birmingham
ID Code:1264
This unpublished thesis/dissertation is copyright of the author and/or third parties.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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