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, Eun Young Choi

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Pages (from-to)1976-1985
Number of pages10
JournalOncotarget
Volume4
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • Del-1
  • Endothelial cell
  • Inflammation
  • P53

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