BAF60a interacts with p53 to recruit the SWI/SNF complex.
To understand the tumor-suppressing mechanism of the SWI/SNF chromatin remodeling complex, we investigated its molecular relationship with p53. Using the pREP4-luc episomal reporter, we first demonstrated that p53 utilizes the chromatin remodeling activity of the SWI/SNF complex to initiate transcription from the chromatin-structured promoter. Among the components of the SWI/SNF ... complex, we identified BAF60a as a mediator of the interaction with p53 by the yeast two-hybrid assay. p53 directly interacted only with BAF60a, but not with other components of the SWI/SNF complex, such as BRG1, SRG3, SNF5, or BAF57. We found out that multiple residues at the amino acid 108-150 region of BAF60a were involved in the interaction with the tetramerization domain of p53. The N-terminal fragment of BAF60a containing the p53-interacting region as well as small interfering RNA for baf60a inhibited the SWI/SNF complex-mediated transcriptional activity of p53. The uncoupling of p53 with the SWI/SNF complex resulted in the repression of both p53-dependent apoptosis and cell cycle arrest by the regulation of target genes. These results suggest that the SWI/SNF chromatin remodeling complex is involved in the suppression of tumors by the interaction with p53.
Mesh Terms:
Amino Acid Sequence, Animals, Apoptosis, Cell Cycle, Cell Line, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, Down-Regulation, Doxorubicin, Humans, Mice, Mutant Proteins, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, Transcription Factors, Transcription, Genetic, Transduction, Genetic, Tumor Suppressor Protein p53
Amino Acid Sequence, Animals, Apoptosis, Cell Cycle, Cell Line, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, Down-Regulation, Doxorubicin, Humans, Mice, Mutant Proteins, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, Transcription Factors, Transcription, Genetic, Transduction, Genetic, Tumor Suppressor Protein p53
J. Biol. Chem.
Date: May. 02, 2008
PubMed ID: 18303029
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