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BAF60a interacts with p53 to recruit the SWI/SNF complex
Jaehak Oh1, Dong H Sohn, Myunggon Ko
1Department of Biological Sciences, Institute of Molecular Biology and Genetics, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, Korea.
The Journal of Biological Chemistry
|February 28, 2008
Summary
The SWI/SNF chromatin remodeling complex interacts with p53 via BAF60a, crucial for tumor suppression. Disrupting this interaction impairs p53
Area of Science:
- Molecular biology
- Cancer research
- Chromatin remodeling
Background:
- The SWI/SNF complex is a chromatin remodeler implicated in tumor suppression.
- The tumor suppressor protein p53 plays a critical role in cellular responses to stress.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying the tumor-suppressing function of the SWI/SNF complex in relation to p53.
- To identify specific interactions between SWI/SNF components and p53.
Main Methods:
- Utilized episomal reporter assays to assess transcriptional activity.
- Employed yeast two-hybrid assays to identify protein-protein interactions.
- Used small interfering RNA (siRNA) to inhibit gene expression.
Main Results:
- p53 requires SWI/SNF chromatin remodeling activity for transcription initiation.
- BAF60a acts as a direct mediator between p53 and the SWI/SNF complex.
- Interaction involves specific residues in BAF60a and the tetramerization domain of p53.
- Disruption of the p53-SWI/SNF interaction abrogated p53-dependent apoptosis and cell cycle arrest.
Conclusions:
- The SWI/SNF complex, through its interaction with p53 mediated by BAF60a, plays a significant role in tumor suppression.
- This interaction is essential for regulating p53 target genes involved in apoptosis and cell cycle control.
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