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PP2A binding proteins and their influence on the cellular phospho-proteome

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Title: PP2A binding proteins and their influence on the cellular phospho-proteome
Authors: Atkin, Sarah
Item Type: Thesis or dissertation
Abstract: PP2A is a major serine/threonine phosphatase in eukaryotic cells which dephosphorylates many of the proteins involved in signal transduction. Alterations in PP2A activity have been implicated in a number of diseases including cancer, which has led to the suggestion that PP2A is a tumor suppressor. PP2A exists in a number of holoenzyme forms. The core dimer (PP2AD) consists of a structural (PR65) and a catalytic (PP2Ac) subunit, and can be associated with one of several regulatory B polypeptides (B, B', B'' and B'''). Interaction with these B subunits probably controls both the subcellular location and substrate specificity of the phosphatase activity. The ST antigen of SV40, and ST and MT antigen of the polyoma tumour virus interact with the PP2A dimer, competing with the B subunits for binding. This interaction has been shown to be required for the full transforming actions of each virus. In addition to the trimeric nature of the holoenzyme, it now clear that many more proteins interact with individual subunits of the PP2A complex, influencing its regulation and activity. Consequently, to understand how viruses affect the regulation and diverse functions of PP2A, it is important to study not only its trimeric state, but also its complex composition. To achieve this, a series of monoclonal antibodies have been generated against the structural subunit of PP2A and two of the regulatory subunits. The characterisation of these antibodies and their use in studying PP2A associated proteins are described in this thesis. In a complementary approach, a novel TAP tagged PR65 subunit has been constructed and used to isolate proteins interacting with PP2A. Associated proteins have been indentified by MS approaches. Interestingly, the deubiquitinating enzyme, USP28, has been shown to interact with PP2AD, in immunoprecipitation experiments. This association appears to affect the ubiquitin status of PP2A.
Issue Date: 2010
Date Awarded: May-2010
URI: http://hdl.handle.net/10044/1/5607
DOI: https://doi.org/10.25560/5607
Supervisor: Dilworth, Steve
Author: Atkin, Sarah
Department: Investigative Science
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Medicine PhD theses

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