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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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

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