Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.697327
Title: To investigate the subcellular localisation of CBP (Creb-binding protein) and its interacting proteins
Author: Ryan, Colm M.
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2006
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Abstract:
CBP (Creb-binding Protein) is a histone acetyltransferase that plays an essential role in RNA-polymerase II-dependent transcription. CBP acetylation of non-histone proteins such as p53, ACTR and Impa has been postulated to regulate their activity. The research described shows the interaction between CBP and the nuclear transport proteins CAS, Impa and the nucleoporin Nup93. We show that increasing global acetylation levels using HDAC inhibitors (HDACi) leads to a perturbation in the subcellular localisation of CAS, while the number of CBP-associated PML bodies increases. In addition, we demonstrate that CBP association with Impa increases in response to HDACi treatment. These results give us a novel insight into the regulation of non-histone proteins by HDACi. In addition, these findings suggest a functional link between chromatin regulation, acetylation and nuclear transport. Mislocalisation of CBP from PML bodies has been implicated in the pathology of many diseases such as Huntingdon's disease and Acute Myeloid leukaemia expressing the fusion protein MOZ-TIF2. CBP mislocalisation has also been implicated in Kennedy's disease, a late onset neurodegenerative disorder, which expresses a mutant form of the Androgen Receptor (AR) with an expanded polyglutamine region. Reports in the literature suggest that the mislocalisation of CBP in Kennedy's disease may play a crucial role in its pathology. Here we describe experiments, which show that both CBP and PML are mislocalised in cell expressing AR with An expanded polyglutamine tract. Furthermore, we demonstrate that ARQ077-dependent transcriptional repression cannot be rescued by overexpression of CBP in neuronal and non-neuronal cell line. These results shed new light on the potential role of CBP and PML in Kennedy's disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.697327  DOI: Not available
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