Acetylation control of the retinoblastoma tumour suppressor protein

Markham, Douglas James (2006) Acetylation control of the retinoblastoma tumour suppressor protein. PhD thesis, University of Glasgow.

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Abstract

The work presented in this thesis concentrates on the functional consequences of acetylation upon the retinoblastoma tumour suppressor protein (pRb), the activity of which is frequently, if not universally, de-regulated in tumour cells. This study has shown that the acetylation of pRb at lysine (K) residues 873/874 reduces the interaction of E2F-1 with the carboxyl terminal (C-terminal) region of pRb. In turn this acetylation event promotes the association of the C-terminal region of pRb with its amino terminal (N-terminal) domain (residues 1-378). A further aspect of this study suggests that acetylation may result in a change of pRb localization from the nucleus to the cytoplasm. Moreover it is also shown that the N-terminal of pRb is acetylated in vitro and in cells. These results suggest a model whereby the acetylation of pRb at E2F-1 target genes results in a reduced interaction between the C-terminal of pRb and E2F-1. Another ramification of the model implies that the N-terminal region of pRb interacts with the C-terminal region in response to DNA damage induced acetylation of pRb. This interaction may influence the bipartite nuclear localization signal (NLS) within the C-terminal domain, thus providing a possible mechanism for retaining pRb localised to the cytoplasm. These results highlight a new mechanism through which pRb may mediate tumour suppressor activity, and in addition define a previously undescribed pathway through which acetylation can influence growth control.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Robert White
Keywords: Molecular biology
Date of Award: 2006
Depositing User: Enlighten Team
Unique ID: glathesis:2006-71747
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 09:31
Last Modified: 17 May 2019 09:31
URI: http://theses.gla.ac.uk/id/eprint/71747

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