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The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival

Clemo, N.K., Arhel, N.J., Barnes, J.D., Baker, J., Moorghen, M., Packham, G.K., Paraskeva, C. and Williams, A.C. (2005) The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival Biochemical Society Transactions, 33, pp. 676-678.

Record type: Article

Abstract

Although the retinoblastoma susceptibility gene RB1 is inactivated in a wide variety of human cancers, the retinoblastoma protein (Rb) has been shown to be overexpressed in colon cancers, which is linked to the anti-apoptotic function of the protein. However, the mechanisms by which Rb regulates apoptosis are yet to be fully elucidated. We have established that Rb interacts with the anti-apoptotic BAG-1 (Bcl-2 associated athanogene-1) protein, and that a decrease in nuclear localization of BAG-1 is detectable when the interaction between Rb and BAG-1 is disrupted by expression of the E7 viral oncoprotein. Interestingly, although reported as deregulated in colorectal cancers, we have found that BAG-1 expression is also altered in small adenomas, where its localization was found to be predominantly nuclear. In addition, we have established that maintenance of high nuclear BAG-1 in vitro increases the resistance of adenoma-derived cells to g-radiation-induced apoptosis. Our work suggests a novel function for Rb, involving modulation of the subcellular localization of BAG-1. We have found predominant nuclear BAG-1 localization in small adenomas, and suggest that BAG-1 may promote colorectal tumour cell survival by making colonic epithelial cells less sensitive to DNA damage.

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More information

Published date: 2005
Keywords: retinoblastoma protein (rb), bag-1, colorectal, adenoma, apoptosis, radiation

Identifiers

Local EPrints ID: 26250
URI: http://eprints.soton.ac.uk/id/eprint/26250
ISSN: 0300-5127
PURE UUID: 50a89802-00ae-4345-950f-3eb4a1d860c3

Catalogue record

Date deposited: 21 Apr 2006
Last modified: 17 Jul 2017 16:08

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Contributors

Author: N.K. Clemo
Author: N.J. Arhel
Author: J.D. Barnes
Author: J. Baker
Author: M. Moorghen
Author: G.K. Packham
Author: C. Paraskeva
Author: A.C. Williams

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