Characterisation of DRAM-1 in vitro and in vivo

Mah, Li Yen (2012) Characterisation of DRAM-1 in vitro and in vivo. PhD thesis, University of Glasgow.

Due to Embargo and/or Third Party Copyright restrictions, this thesis is not available in this service.

Abstract

Autophagy is a cellular housekeeping process that drives the degradation of intracellular and extracellular components in the lysosomes. Defects in this process have been implicated with many diseases, among them cancer. Damage-Regulated Autophagy Modulator (DRAM-1) is a p53 target gene that has been shown to regulate autophagy, and it is believed to act as a tumour suppressor. In addition to the full-length transcript (splice variant 1) that has previously been characterised, multiple splice isoforms of DRAM-1 have been identified. The first part of this thesis focuses on the investigation of the properties of the DRAM-1 isoforms 1, 4 and 5. These isoforms are localised to different cellular compartments. DRAM-1 isoforms are highly specific regulators of autophagy. They neither mediate the turnover of long-lived proteins nor do they decrease enhanced intracellular reactive oxygen species (ROS). Although activation of DRAM-1 on its own does not promote cell death, it is required for effective p53-mediated cell death in vitro. The next step was to proceed to the characterisation of the cellular function of DRAM-1 in vivo. In the final part of the thesis, the role of DRAM-1 in mediating T cell activation was examined. In summary, these results contribute to the understanding of how autophagy is regulated by DRAM-1, and uncover novel roles for p53 and DRAM-1 beyond cell death and autophagy regulation. Still, these pathways necessitate further investigation and harness a great potential to be targeted therapeutically to enhance tumour cell death.

Item Type:	Thesis (PhD)
Qualification Level:	Doctoral
Additional Information:	Due to copyright restrictions the full text of this thesis cannot be made available online. Access to the printed version is available once any embargo periods have expired.
Keywords:	DRAM-1, autophagy, in vivo, in vitro
Subjects:	UNSPECIFIED
Colleges/Schools:	College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Supervisor's Name:	Ryan, Prof. Kevin
Date of Award:	2012
Embargo Date:	14 November 2015
Depositing User:	Dr. Li Yen Mah
Unique ID:	glathesis:2012-3751
Copyright:	Copyright of this thesis is held by the author.
Date Deposited:	26 Nov 2012
Last Modified:	10 Dec 2012 14:10
URI:	http://theses.gla.ac.uk/id/eprint/3751

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