Characterisation of novel PRMT1 interacting proteins AND Hepatocyte-Lymphocyte cell-in-cell structures: Implications for the host cell

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Davies, Scott Philip (2014). Characterisation of novel PRMT1 interacting proteins AND Hepatocyte-Lymphocyte cell-in-cell structures: Implications for the host cell. University of Birmingham. M.Res.

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Abstract

Protein arginine methylation has become of interest in recent years for its involvement in diverse cellular processes. This modification is catalysed by protein arginine methyltransferases (PRMTs). PRMT1 is the predominant methyltransferase in eukaryotes, performing 85% of all cellular arginine methylation. There are 7 known PRMT1 splice-variants which vary in cellular localisation and activity. Several physiological processes, including gene expression and cellular signalling, have been shown to involve PRMT1. Furthermore, PRMT1 is upregulated in several cancers and its direct involvement in progression of leukaemia and ERα-driven breast cancers is evident. Information regarding PRMT1 regulation is lacking. The Davies laboratory recently discovered potential interactions between PRMT1v1 and two enzymes involved in post-translational protein modification which we have named PBP (PRMT1-binding protein) 1 and 2. However, it was unknown if these interactions were direct or indirect. To address this, we generated recombinant proteins of His-SUMO-PRMT1v2, and GST-PBP1 and GST-PBP2 for use within pull-down protein-interaction assays. Both GST-PBP1 and GST-PBP2 were capable of direct interaction with His-SUMO-PRMT1v2. These interactions were not seen under non-physiological NaCl levels, suggesting that such events could occur in vivo. It is unconfirmed if such interactions are enzyme-substrate events or whether they regulate protein activity through direct binding. Once this is elucidated, intervention of these interactions could be of therapeutic and anti-tumourigenic importance.

Type of Work: Thesis (Masters by Research > M.Res.)
Award Type: Masters by Research > M.Res.
Supervisor(s):
Supervisor(s)EmailORCID
Davis, ClaireUNSPECIFIEDUNSPECIFIED
Stamataki, ZaniaUNSPECIFIEDUNSPECIFIED
Licence:
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Immunity and Infection
Funders: Medical Research Council
Subjects: R Medicine > RC Internal medicine
URI: http://etheses.bham.ac.uk/id/eprint/5285

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