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

• Published in: International journal of cancer Vol. 106; no. 3; pp. 364 - 371
• Main Authors: Arhel, Nathalie J., Packham, Graham, Townsend, Paul A., Collard, Tracey J., H‐Zadeh, Akram M., Sharp, Adam, Cutress, Ramsey I., Malik, Karim, Hague, Angela, Paraskeva, Chris, Williams, Ann C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-09-2003; Wiley-Liss; Wiley
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenoma - genetics; Adenoma - metabolism; Adenoma - pathology; Bag‐1; Biological and medical sciences; Blotting, Western; Cancer; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Death; Cell Nucleus - metabolism; colon; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; DNA-Binding Proteins; Epithelial Cells; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Vectors; Glutathione Transferase - metabolism; human; Humans; interaction; Life Sciences; Medical sciences; Microscopy, Confocal; Oncogene Proteins, Viral - genetics; Papillomavirus E7 Proteins; Precipitin Tests; Protein Transport; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; retinoblastoma; Retinoblastoma Protein - genetics; Retinoblastoma Protein - metabolism; Saccharomyces cerevisiae; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Subcellular Fractions; Transcription Factors; Tumor Cells, Cultured; Tumors; Two-Hybrid System Techniques; Human; Carcinoma; Retinoblastoma gene; Interaction; Malignant tumor; Adenoma; Protein; Colonic disease; Regulation(control); Cell death; Established cell line; Digestive diseases; Genetics; Intestinal disease; Benign neoplasm; Colon; Apoptosis; Tumor suppressor gene
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11257

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. © 2003 Wiley‐Liss, Inc.