Investigating Polo-like kinase 4-regulated signalling using SILAC-based quantitative phosphoproteomics


Ferries, Samantha (2019) Investigating Polo-like kinase 4-regulated signalling using SILAC-based quantitative phosphoproteomics. PhD thesis, University of Liverpool.

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Abstract

Protein phosphorylation plays a critical role in regulating cellular responses, including the coordination of cell division. Polo-like kinase 4 (PLK4), a cell cycle regulated Ser/Thr protein kinase, is the master regulator of centriole biogenesis, a process required for formation of the biopolar mitotic spindle. PLK4 expression and activity are both very tightly controlled, and dysregulation leads to aberrant centrosome duplication resulting in chromosome missegregation and aneuploidy. Despite its rising importance as a potential anti-cancer target, few PLK4 substrates have been identified, and much remains to be understood about basic PLK4 biology at the centrosome, and wider potential roles within the cell. The experiments described in this thesis focused on an evaluation of PLK4 signalling, exploiting SILAC-based quantitative phosphoproteomics and the protein kinase inhibitor centrinone to probe cellular function. Initially, I describe the development of biochemical tools to study PLK4-dependent signalling, and its inhibition by centrinone. This included the generation of stable isogenic U2OS cell lines, transfected with either WT PLK4 or a centrinone-resistant G95R PLK4 mutant. The G95R PLK4 cell line ... (continues)

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 29 Mar 2019 09:37
Last Modified: 08 Feb 2025 01:52
DOI: 10.17638/03032694
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3032694
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