Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.514559
Title: PP2A binding proteins and their influence on the cellular phospho-proteome
Author: Atkin, Sarah
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2010
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
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.
Supervisor: Dilworth, Steve Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.514559  DOI: Not available
Share: