Angiotensin-converting enzyme Ance is cooperatively regulated by Mad and Pannier in Drosophila imaginal discs. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Kim, Ah-Ram; Choi, Eun-Bee; Kim, Mi-Young; Choi, Kwang-Wook
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 17
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-13487-w
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Angiotensin-converting enzyme (ACE) is an evolutionarily conserved peptidyl dipeptidase. Mammalian ACE converts angiotensin I to the active vasoconstrictor angiotensin II, thus playing a critical role for homeostasis of the renin-angiotensin system. InDrosophila, the ACE homolog Ance is expressed in specific regions of developing organs, but its regulatory mechanism has not been identified. Here we provide evidence thatAnce expression is regulated by a combination of Mad and Pannier (Pnr) in imaginal discs. We demonstrate thatAnce expression in eye and wing discs depends on Dpp signaling. The Mad binding site ofAnce regulatory region is essential forAnce expression.Ance expression in imaginal discs is also regulated by the GATA family transcription factor Pnr. Pnr directly regulatesAnce expression by binding to a GATA site ofAnce enhancer. In addition, Pnr and Mad physically and genetically interact.Ance null mutants are morphologically normal but show genetic interaction withdpp mutants. Furthermore, we show that human SMAD2 and GATA4 physically interact andACE expression in HEK293 cells is regulated by SMAD2 and GATA4. Taken together, this study reveals a cooperative mechanism ofAnce regulation by Mad and Pnr. Our data also suggest a conserved transcriptional regulation of humanACE .