Investigating the relationship between Survivin and Tank-Binding Kinase 1 in cancer cells

Daly, Lauren (2021) Investigating the relationship between Survivin and Tank-Binding Kinase 1 in cancer cells. MRes thesis, University of Nottingham.

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Survivin is a multi-functional, homeostatic regularity protein with opposing roles in cell proliferation and cell death. Survivin overexpression is a key biomarker for the identification of oncogenic cells. Within cancer, survivin is contributes to the inhibition of cell death and dysregulation of proliferation. Within the cell, survivin is either located with the DNA during mitosis or within the cytoplasm. However, a unique oncogenic pool of survivin has been found within the mitochondria. Evidence has shown that the mitochondrial pool of survivin is linked to the inhibition of apoptosis. However, it is still unknown how this pool of survivin develops.

The aim of this thesis was to determine whether survivin is a novel substrate of TBK1 phosphorylation and whether TBK1 regulates survivin function within cancer cells. Through bioinformatics, a putative TBK1 phosphorylation site was found at threonine 5 within the mitochondrial targeting sequence of survivin. Moreover, mutant studies showed that phosphorylation at this site resulted in an increase in binucleation and exclusion of survivin from the mitochondria. Interaction assays showed that TBK1 binds directly to survivin within its N-terminus. Whether TBK1 is the kinase which regulates survivins function within cancer still needs to be determined. Collectively, this thesis has shown insight into how the mitochondrial pool of survivin accumulates and a novel binding partner for survivin.

Item Type: Thesis (University of Nottingham only) (MRes)
Supervisors: Wheatley, Sally
Keywords: Cancer, Mitochondria, Mitosis, Survivin, Tank-binding kinase
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: 67055
Depositing User: Daly, Lauren
Date Deposited: 08 Dec 2021 04:40
Last Modified: 08 Dec 2022 04:30

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