Samuelson, A. V., Narita, M., Chan, H. M., Jin, J., de Stanchina, E., McCurrach, M. E., Narita, M., Fuchs, M., Livingston, D. M., Lowe, S. W. (June 2005) p400 is required for E1A to promote apoptosis. J Biol Chem, 280 (23). pp. 21915-23. ISSN 0021-9258 (Print)
Abstract
The adenovirus E1A oncoprotein promotes proliferation and transformation by binding cellular proteins, including members of the retinoblastoma protein family, the p300/CREB-binding protein transcriptional coactivators, and the p400-TRRAP chromatin-remodeling complex. E1A also promotes apoptosis, in part, by engaging the ARF-p53 tumor suppressor pathway. We show that E1A induces ARF and p53 and promotes apoptosis in normal fibroblasts by physically associating with the retinoblastoma protein and a p400-TRRAP complex and that its interaction with p300 is largely dispensable for these effects. We further show that E1A increases p400 expression and, conversely, that suppression of p400 using stable RNA interference reduces the levels of ARF, p53, and apoptosis in E1A-expressing cells. Therefore, whereas E1A inactivates the retinoblastoma protein, it requires p400 to efficiently promote cell death. These results identify p400 as a regulator of the ARF-p53 pathway and a component of the cellular machinery that couples proliferation to cell death.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | ADP-Ribosylation Factors metabolism Adenovirus E1A Proteins metabolism physiology Animals E1A Apoptosis Binding Sites Blotting Northern Blotting Western Cell Line Cell Survival Chromatin metabolism DNA Helicases metabolism physiology DNA-Binding Proteins metabolism physiology Dose-Response Relationship Drug Doxorubicin pharmacology E1A-Associated p300 Protein Fibroblasts metabolism Gene Deletion Gene Expression Regulation Gene Transfer Techniques Genetic Vectors Humans Immunoblotting Immunoprecipitation Mice Microscopy Fluorescence Mutation Nuclear Proteins metabolism Protein Binding Protein Structure Tertiary RNA Interference Retinoblastoma Protein metabolism Retroviridae genetics Structure-Activity Relationship Trans-Activation Trans-Activators metabolism Tumor Suppressor Protein p53 metabolism |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis |
| CSHL Authors: | |
| Communities: | CSHL labs > Lowe lab |
| Depositing User: | CSHL Librarian |
| Date: | 10 June 2005 |
| Date Deposited: | 06 Jan 2012 18:36 |
| Last Modified: | 06 Jan 2012 18:36 |
| URI: | https://repository.cshl.edu/id/eprint/22692 |
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