The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival. (1st August 2005)

• Record Type: Journal Article
• Authors: Clemo, N.K.; Arhel, N.J.; Barnes, J.D.; Baker, J.; Moorghen, M.; Packham, G.K.; Paraskeva, C.; Williams, A.C.
• Is Part Of: Biochemical Society transactions. Volume 33:Number 4(2005)
• Page Start: 676
• Page End: 678
• Publication Date: 2005-08-01
• Subjects: retinoblastoma protein (Rb) -- BAG-1 -- colorectal -- adenoma -- apoptosis -- radiation; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0330676
• Languages: English
• ISSNs: 0300-5127

Abstract

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 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.