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

// Hyesoon Kim 1 , Seung-Hwan Lee 1 , Mi-Ni Lee 2 , Goo Taeg Oh 2 , Kyung-Chul Choi 1,3 and Eun Young Choi 1,3 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.