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

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 p...

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Main Author: Daly, Lauren
Format: Thesis (University of Nottingham only)
Language:English
Published: 2021
Subjects:
Online Access:https://eprints.nottingham.ac.uk/67055/
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author Daly, Lauren
author_facet Daly, Lauren
author_sort Daly, Lauren
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-670552025-02-28T15:13:53Z https://eprints.nottingham.ac.uk/67055/ Investigating the relationship between Survivin and Tank-Binding Kinase 1 in cancer cells Daly, Lauren 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. 2021-12-08 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/67055/1/Investigating%20the%20relationship%20between%20Survivin%20and%20Tank-Binding%20Kinase%201%20in%20cancer%20cells.pdf Daly, Lauren (2021) Investigating the relationship between Survivin and Tank-Binding Kinase 1 in cancer cells. MRes thesis, University of Nottingham. Cancer Mitochondria Mitosis Survivin Tank-binding kinase
spellingShingle Cancer
Mitochondria
Mitosis
Survivin
Tank-binding kinase
Daly, Lauren
Investigating the relationship between Survivin and Tank-Binding Kinase 1 in cancer cells
title Investigating the relationship between Survivin and Tank-Binding Kinase 1 in cancer cells
title_full Investigating the relationship between Survivin and Tank-Binding Kinase 1 in cancer cells
title_fullStr Investigating the relationship between Survivin and Tank-Binding Kinase 1 in cancer cells
title_full_unstemmed Investigating the relationship between Survivin and Tank-Binding Kinase 1 in cancer cells
title_short Investigating the relationship between Survivin and Tank-Binding Kinase 1 in cancer cells
title_sort investigating the relationship between survivin and tank-binding kinase 1 in cancer cells
topic Cancer
Mitochondria
Mitosis
Survivin
Tank-binding kinase
url https://eprints.nottingham.ac.uk/67055/