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BASP1 is a transcriptional cosuppressor for the Wilms' tumor suppressor protein WT1
Brian Carpenter1, Kathryn J Hill, Marika Charalambous
1School of Biological Sciences, University of Manchester, G.186 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Abstract:
The Wilms' tumor suppressor protein WT1 is a transcriptional regulator that plays a key role in the development of the kidneys. The transcriptional activation domain of WT1 is subject to regulation by a suppression region within the N terminus of WT1. Using a functional assay, we provide direct evidence that this requires a transcriptional cosuppressor, which we identify as brain acid soluble protein 1 (BASP1). WT1 and BASP1 associate within the nuclei of cells that naturally express both proteins. BASP1 can confer WT1 cosuppressor activity in transfection assays, and elimination of endogenous BASP1 expression augments transcriptional activation by WT1. BASP1 is present in the developing nephron structures of the embryonic kidney and, coincident with that of WT1, its expression is restricted to the highly specialized podocyte cells of the adult kidney. Taken together, our results show that BASP1 is a WT1-associated factor that can regulate WT1 transcriptional activity.
Insights
Brain acid-soluble protein 1 (BASP1) acts as a crucial cosuppressor for the Wilms' tumor suppressor protein (WT1). This discovery reveals a new regulatory mechanism in kidney development and WT1 transcriptional activity.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- The Wilms' tumor suppressor protein (WT1) is a critical transcriptional regulator in kidney development.
- WT1's transcriptional activation is modulated by an N-terminal suppression region.
Purpose of the Study:
- To identify the factors involved in WT1-mediated transcriptional repression.
- To elucidate the role of novel interacting proteins in WT1 function.
Main Methods:
- Functional assays to test for cosuppressor activity.
- Co-immunoprecipitation to assess protein-protein interactions.
- Transfection assays to evaluate regulatory effects.
- Immunohistochemistry to determine protein localization in embryonic and adult kidneys.
Main Results:
- Brain acid-soluble protein 1 (BASP1) was identified as a WT1 transcriptional cosuppressor.
- WT1 and BASP1 form nuclear complexes in cells expressing both proteins.
- BASP1 expression is required for WT1 cosuppressor activity; its elimination enhances WT1 activation.
- BASP1 is localized in developing nephrons and adult podocytes, mirroring WT1 expression patterns.
Conclusions:
- BASP1 is a key WT1-associated factor that regulates WT1 transcriptional activity.
- BASP1 plays a significant role in the biological functions of WT1, particularly in kidney development.
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