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
J. Biol. Chem.
Date: May. 02, 2008
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