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Tumor suppressor U19/EAF2 regulates thrombospondin-1 expression via p53
F Su1, L E Pascal, W Xiao
1Department of Urology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Oncogene
|October 15, 2009
Summary
Loss of U19/EAF2 protein promotes cancer by down-regulating thrombospondin-1 (TSP-1). U19/EAF2 blocks p53 from repressing TSP-1, thus maintaining its expression and inhibiting tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- U19/EAF2 inactivation is linked to tumorigenesis across multiple organs.
- The precise mechanism of U19/EAF2's tumor suppressor function is not fully understood.
- Thrombospondin-1 (TSP-1) is an anti-angiogenic protein whose expression is critical in tumor suppression.
Purpose of the Study:
- To elucidate the mechanism by which U19/EAF2 suppresses tumors.
- To investigate the role of U19/EAF2 in regulating thrombospondin-1 (TSP-1) expression.
- To determine the interaction between U19/EAF2, p53, and the TSP-1 promoter.
Main Methods:
- Analysis of TSP-1 expression and angiogenesis markers (CD31) in U19/EAF2 knockout mice.
- Co-localization and co-immunoprecipitation assays to study protein interactions.
- Luciferase reporter assays to assess TSP-1 promoter activity modulated by p53 and U19/EAF2.
Main Results:
- U19/EAF2 knockout mice exhibited down-regulated TSP-1 expression in prostate and liver tissues.
- Increased angiogenesis, indicated by elevated CD31-positive blood vessels, was observed in U19/EAF2 knockout livers.
- U19/EAF2 was found to co-localize and co-immunoprecipitate with p53.
- U19/EAF2 blocked p53-mediated repression of the TSP-1 promoter activity.
Conclusions:
- U19/EAF2 functions as a tumor suppressor by regulating TSP-1 expression.
- The mechanism involves U19/EAF2 preventing p53 from repressing the TSP-1 promoter.
- These findings highlight a novel regulatory pathway involving U19/EAF2, p53, and TSP-1 in cancer suppression.
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