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 γ-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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Conference Article|
August 01 2005
The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival
N.K. Clemo;
N.K. Clemo
*Department of Pathology and Microbiology, Bristol University, Bristol B58 1TD, U.K.
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N.J. Arhel;
N.J. Arhel
*Department of Pathology and Microbiology, Bristol University, Bristol B58 1TD, U.K.
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J.D. Barnes;
J.D. Barnes
*Department of Pathology and Microbiology, Bristol University, Bristol B58 1TD, U.K.
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J. Baker;
J. Baker
*Department of Pathology and Microbiology, Bristol University, Bristol B58 1TD, U.K.
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M. Moorghen;
M. Moorghen
†Department of Pathology and Histology, Bristol Royal Infirmary, Bristol, U.K.
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G.K. Packham;
G.K. Packham
‡Cancer Research UK Oncology Unit, University of Southampton, Southampton SO16 1TD, U.K.
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C. Paraskeva;
C. Paraskeva
*Department of Pathology and Microbiology, Bristol University, Bristol B58 1TD, U.K.
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A.C. Williams
A.C. Williams
1
*Department of Pathology and Microbiology, Bristol University, Bristol B58 1TD, U.K.
1To whom correspondence should be addressed (email Ann.C.Williams@bristol.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 14 2005
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2005 The Biochemical Society
2005
Biochem Soc Trans (2005) 33 (4): 676–678.
Article history
Received:
March 14 2005
Citation
N.K. Clemo, N.J. Arhel, J.D. Barnes, J. Baker, M. Moorghen, G.K. Packham, C. Paraskeva, A.C. Williams; The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival. Biochem Soc Trans 1 August 2005; 33 (4): 676–678. doi: https://doi.org/10.1042/BST0330676
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