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Prohibitin is required for transcriptional repression by the WT1-BASP1 complex
E Toska1, J Shandilya1, S J Goodfellow2
1Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA.
Oncogene
|October 30, 2013
Summary
The Wilms tumor-1 protein (WT1) and BASP1 form a complex with prohibitin, a transcriptional repressor. This complex recruits chromatin remodeling factors, impacting gene regulation.
Area of Science:
- Molecular Biology
- Gene Regulation
- Transcriptional Control
Background:
- Wilms tumor-1 protein (WT1) regulates genes involved in cell growth, apoptosis, and differentiation.
- BASP1, a corepressor, mediates WT1's transcriptional repression activity and functions within large complexes.
Purpose of the Study:
- To investigate the role of prohibitin in the WT1-BASP1 transcriptional repression complex.
- To elucidate the mechanism by which the WT1-BASP1 complex regulates gene expression.
Main Methods:
- Co-immunoprecipitation to identify protein interactions.
- Immunofluorescence to determine subcellular localization.
- Chromatin immunoprecipitation to assess promoter recruitment.
- Analysis of phospholipid association and recruitment of cofactors.
Main Results:
- Prohibitin interacts with BASP1 and is recruited to WT1 target gene promoters, mediating BASP1-dependent repression.
- Prohibitin and BASP1 cooperate to recruit BRG1, a chromatin remodeling factor, leading to CBP dissociation.
- The BASP1-prohibitin complex facilitates PIP2 and HDAC1 recruitment to WT1 target genes.
Conclusions:
- Prohibitin is a component of the WT1-BASP1 transcriptional repression complex.
- The BASP1-prohibitin complex plays a critical role in recruiting chromatin remodeling factors, including BRG1 and HDAC1.
- This complex mediates PIP2-dependent transcriptional repression of WT1 target genes, offering new insights into prohibitin's function.
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