The role of survivin in autophagy

Humphry, Nicola (2018) The role of survivin in autophagy. PhD thesis, University of Nottingham.

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Abstract

Survivin is a highly conserved protein with important roles in cell death and mitosis; deletion of the survivin gene is embryonically lethal. It is highly expressed in most cancers, making it a promising target for cancer therapy. Autophagy, an important homeostatic cellular recycling system, promotes cell survival under stresses such as DNA damage, nutrient starvation and hypoxia.

Recent research has begun to identify a link between survivin and autophagy, and therefore the aim of this thesis was to clarify the role of survivin in autophagy and to study the reported interaction between survivin and the autophagic protein microtubule-associated protein light chain 3 (LC3).

To achieve this aim, a variety of cell biology and molecular biology techniques were employed. Cultured human cells were modified to express survivin and LC3 with fluorescent tags and studied with fluorescence microscopy to investigate the localisation and characteristics of both survivin and autophagic bodies. Co-immunoprecipitation was used to study the interaction between survivin and LC3, and gene manipulation was used to identify the critical amino acid residues.

This thesis reports that high levels of survivin reduce the rate of autophagy and are associated with smaller autophagic bodies and larger acidic bodies. In addition, this study reveals that survivin interacts with LC3 through a canonical LC3-interaction region at residues 61-64, but this interaction is not critical to the role of survivin in regulating autophagosome or acidic body size. Finally, it raises the possibility that survivin-LC3 interaction may affect the mitotic role of survivin.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Wheatley, S.P.
Huett, A.
Keywords: Survivin; lc3; Autophagy; Mitosis
Subjects: Q Science > QR Microbiology > QR180 Immunology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 55462
Depositing User: Humphry, Nicola
Date Deposited: 12 Apr 2019 12:57
Last Modified: 07 May 2020 13:45
URI: http://eprints.nottingham.ac.uk/id/eprint/55462

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