Investigating how survivin expression affects the cell death response induced by UV irradiation

Coe, Kirstie Danielle (2020) Investigating how survivin expression affects the cell death response induced by UV irradiation. MRes thesis, University of Nottingham.

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Abstract

Survivin is a multi-functional protein with documented roles in both cell death and proliferation. Over-expression of survivin has been observed in several cancer types and due to its pro-survival activities, it is an ideal target for onotherapy. However, there are still many unanswered questions surrounding the role of survivin in cancer. Furthermore, a cancer specific mitochondrial pool of survivin exists that is thought to be important for its role in inhibiting apoptosis, as the mitochondria are common sites for apoptosis initiation. To support this, previous research has shown that removal of its bona fide mitochondrial targeting sequence represses the anti-apoptotic function of survivin. Therefore, the aim of this thesis was to investigate the role of mitochondrial survivin in protecting cancerous cells from UV-induced apoptosis.

When assayed for its ability to inhibit apoptosis, wild-type survivin showed a greater reluctance to enter the intrinsic pathway when compared to control cells. Furthermore, of those cells that entered apoptosis, only a small proportion died as a result. However, immunoassays identified a reduction in the fission protein DRP1 in untreated Svn1-10GFP samples, but a significant increase following exposure to UVC. Elevated DRP1 was initially thought to promote mitochondrial fission, an early step in the intrinsic pathway, but fluorescence microscopy revealed no difference between the mitochondrial networks of cells expressing GFP and SvnGFP. Collectively, the data presented highlights a potential role for mitochondrial survivin in apoptosis inhibition through its ability to alter mitochondrial metabolism and interact with several proteins involved in both the intrinsic pathway and anastasis.

Item Type: Thesis (University of Nottingham only) (MRes)
Supervisors: Wheatley, Sally
Bennett, Andrew
Keywords: Survivin, Cancer, Apoptosis, Mitochondria, Cytochrome c, UV
Subjects: Q Science > QH Natural history. Biology > QH573 Cytology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 59692
Depositing User: Coe, Kirstie
Date Deposited: 04 Aug 2020 09:05
Last Modified: 04 Aug 2020 09:05
URI: http://eprints.nottingham.ac.uk/id/eprint/59692

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