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Tumor suppressor U19/EAF2 regulates thrombospondin-1 expression via p53

Abstract

Inactivation of U19/EAF2 has been shown previously to lead to tumorigenesis in multiple organs; however, the mechanism of U19/EAF2 tumor suppression remains unclear. In this paper, we report that the expression of an anti-angiogenic protein, thrombospondin-1 (TSP-1) is down-regulated in the prostate and liver of U19/EAF2 knockout mouse. The U19/EAF2 knockout liver displayed increased CD31-positive blood vessels, suggesting that the TSP-1 down-regulation can contribute to increased angiogenesis. TSP-1 is reported to be a p53-target gene and p53 is a known binding partner of ELL, which binds to U19/EAF2. Here, we show that U19/EAF2 can co-localize and co-immunoprecipitate with p53 in transfected cells. In a TSP-1 promoter-driven luciferase reporter assay, p53 transfection suppressed the TSP-1 promoter activity and U19/EAF2 co-transfection blocked the p53 suppression of TSP-1 promoter. However, U19/EAF2 transfection alone had little or no effect on the TSP-1 promoter. The above observations together suggest that U19/EAF2 regulates the expression of TSP-1 via blocking p53 repression of the TSP-1 promoter.

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Acknowledgements

This work was supported in part by NIH Grant Number R01 CA 120386, R37 DK51993, and Prostate Cancer Specialized Program of Research Excellence (SPORE), P50 CA90386.

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Correspondence to Z Wang.

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Su, F., Pascal, L., Xiao, W. et al. Tumor suppressor U19/EAF2 regulates thrombospondin-1 expression via p53. Oncogene 29, 421–431 (2010). https://doi.org/10.1038/onc.2009.326

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