title: The retinoblastoma protein interacts with Bag-1 in human colonic adenoma and carcinoma derived cell lines.
abstract: Although the retinoblastoma susceptibility gene RB1 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 colonic 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.
authors.affiliation: Cancer Research UK Colorectal Tumour Biology Research Group, Department of Pathology and Microbiology, University of Bristol, School of Medical Sciences, Bristol BS8 1TD, United Kingdom.
authors.forename: Nathalie J
authors.initials: NJ
authors.lastname: Arhel
authors.forename: Graham
authors.initials: G
authors.lastname: Packham
authors.forename: Paul A
authors.initials: PA
authors.lastname: Townsend
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Collard
authors.forename: Akram M
authors.initials: AM
authors.lastname: H-Zadeh
authors.forename: Adam
authors.initials: A
authors.lastname: Sharp
authors.forename: Ramsey I
authors.initials: RI
authors.lastname: Cutress
authors.forename: Karim
authors.initials: K
authors.lastname: Malik
authors.forename: Angela
authors.initials: A
authors.lastname: Hague
authors.forename: Chris
authors.initials: C
authors.lastname: Paraskeva
authors.forename: Ann C
authors.initials: AC
authors.lastname: Williams
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins; D004847:Epithelial Cells; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D011233:Precipitin Tests; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D013347:Subcellular Fractions; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
chemical_list: C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16; D005982:Glutathione Transferase