Oncotarget

Research Papers:

p53 regulates the transcription of the anti-inflammatory molecule developmental endothelial locus-1 (Del-1)

Hyesoon Kim, Seung-Hwan Lee, Mi-Ni Lee, Goo Taeg Oh, Kyung-Chul Choi and Eun Young Choi _

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Oncotarget. 2013; 4:1976-1985. https://doi.org/10.18632/oncotarget.1318

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Abstract

Hyesoon Kim1, Seung-Hwan Lee1, Mi-Ni Lee2, Goo Taeg Oh2, Kyung-Chul Choi1,3 and Eun Young Choi1,3

1 Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea,

2 Division of Life Sciences, Ewha Womans University, Seoul, Republic of Korea,

3 Department of Pharmacology, University of Ulsan College of Medicine, Seoul, Republic of Korea

Correspondence:

Eun Young Choi, email:

Keywords: p53, inflammation, endothelial cell, Del-1

Received: August 23, 2013 Accepted: October 1, 2013 Published: October 3, 2013

Abstract

Developmental endothelial locus-1 (Del-1) is an endothelium-derived anti-inflammatory molecule that is downregulated by inflammatory stimuli. Little is known about the molecular mechanisms by which Del-1 transcription is regulated. In the present study, a DNA sequence upstream of the Del-1 gene was analyzed and putative p53 response elements (p53REs) were identified. An approximately 2 kb fragment upstream of the translation start site displayed the highest Del-1 transcriptional activity, and the transcriptional activity of this fragment was enhanced by overexpression of p53. Chemical activation of endogenous p53 elevated the levels of Del-1 mRNA. Site-directed mutagenesis of CATG in the consensus sequences of the 2 kb fragment to TATA significantly reduced the transcription of Del-1. Chromatin immunoprecipitation revealed recruitment of p53 to the p53REs of the Del-1 promoter, resulting in increased Del-1 transcription. Finally, primary endothelial cells isolated from mice with reduced levels of p53 showed a decrease in Del-1 mRNA compared to wild-type endothelial cells. Moreover, Del-1 reciprocally enhanced p53 expression in primary endothelial cells. Thus, these findings suggest that Del-1 is a novel transcriptional target gene of p53.


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