Tumor suppressor U19/EAF2 regulates thrombospondin-1 expression via p53.
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.
Su
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Department of Urology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Pascal
L E
LE
Xiao
W
W
Wang
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Z
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011467:Prostate / Q000378:metabolism; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C472771:EAF2 protein, human; C483108:FESTA protein, mouse; D008164:Luminescent Proteins; D009687:Nuclear Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019700:Thrombospondin 1; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53