title: SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription.
abstract: The SWI/SNF complex is required for the transcription of several genes and has been shown to alter nucleosome structure in an ATP-dependent manner. The tumor suppressor protein p53 displays growth and transformation suppression functions that are frequently lost in mutant p53 proteins detected in various cancers. Using genetic and biochemical approaches, we show that several subunits of the human SWI/SNF complex bind to the tumor suppressor protein p53 in vivo and in vitro. The transactivation function of p53 is stimulated by overexpression of hSNF5 and BRG-1 and dominant forms of hSNF5 and BRG-1 repress p53-dependent transcription. Chromatin immunoprecipitation assay shows that hSNF5 and BRG-1 are recruited to a p53-dependent promoter in vivo. Overexpression of dominant negative forms of either hSNF5 or BRG-1 inhibited p53-mediated cell growth suppression and apoptosis. Molecular connection between p53 and the SWI/SNF complex implicates that (i) the SWI/SNF complex is necessary for p53-driven transcriptional activation, and (ii) the SWI/SNF complex plays an important role in p53-mediated cell cycle control.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Daeyoup
authors.initials: D
authors.lastname: Lee
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Taegun
authors.initials: T
authors.lastname: Seo
authors.forename: Sun Gwan
authors.initials: SG
authors.lastname: Hwang
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
authors.forename: Joonho
authors.initials: J
authors.lastname: Choe
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005799:Genes, Dominant; D005982:Glutathione Transferase / Q000378:metabolism; D005990:Glycerol / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000255:Adenosine Triphosphate; D008156:Luciferases; D005982:Glutathione Transferase; D001616:beta-Galactosidase; D000251:Adenosine Triphosphatases; C084108:SMARCA4 protein, human; D004265:DNA Helicases; D005990:Glycerol