The retinoblastoma protein interacts with Bag-1 in human colonic adenoma and carcinoma derived cell lines

Nathalie J. Arhel, Graham Packham, Paul A. Townsend, Tracey J. Collard, Akram M. H-Zadeh, Adam Sharp, Ramsey I. Cutress, Karim Malik, Angela Hague, Chris Paraskeva, Ann C. Williams

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Although the retinoblastoma susceptibility gene RBI is inactivated in a wide range of human tumours, overexpression in colonic carcinomas has been linked to the antiapoptotic function of the protein. In the current study we show that the Retinoblastoma susceptibility protein (Rb) protein interacts with Bag-1, an apoptotic regulator, in human co-Ionic adenoma- and carcinoma-derived cell lines. Coimmunoprecipitation demonstrated that endogenous Rb and Bag-1 interact in both adenoma- and carcinoma-derived cell lines. The specificity of the interaction was demonstrated by expression of human Papillomavirus E7 oncoprotein, an inhibitor of Rb protein interactions, which disrupted the Rb/ Bag-1 complex. We report that Bag-1 is predominantly localised in the nucleus of colorectal adenoma- and carcinoma-derived epithelial cells. Disruption of the Rb/Bag-1 complex through expression of E7 changes the subcellular distribution of Bag-1, decreasing nuclear localised Bag-1. Our work establishes that the Rb protein interacts with the Bag-1 apoptotic regulator protein, and introduces a novel function for Rb, involving modulation of the subcellular localisation of Bag-1 in human colonic epithelial cells. © 2003 Wiley-Liss, Inc.
    Original languageEnglish
    Pages (from-to)364-371
    Number of pages7
    JournalInternational Journal of Cancer
    Volume106
    Issue number3
    DOIs
    Publication statusPublished - 1 Sep 2003

    Keywords

    • Bag-1
    • Colon
    • Human
    • Interaction
    • Retinoblastoma

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