Synergistic activation of the human adrenomedullin gene promoter by Sp1 and AP-2α

Yan Zhang, Yin Li, Shigeki Shibahara, Kazuhiro Takahashi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Adrenomedullin (AM) is a potent vasodilator peptide, which is ubiquitously expressed and has various biological actions, such as proliferative action and anti-oxidative stress action. AM expression is induced by various stresses, such as hypoxia and inflammatory cytokines, and during cell differentiation. The human AM gene promoter region (-70/-29) contains binding sites for stimulatory protein 1 (Sp1) and activator protein-2α (AP-2α), and has been shown to be important for the AM gene expression during cell differentiation to macrophages or adipocytes. We here show that Sp1 and AP-2α synergistically activate the AM gene promoter. Co-transfection of the reporter plasmid containing the AM promoter region (-103/-29) with Sp1 and AP-2α expression plasmids showed that Sp1 and AP-2α synergistically increased the promoter activity in HeLa cells. Sp1 or AP-2α alone caused only small increases in the promoter activity. EMSA showed that Sp1 bound to the promoter region (-70/-29), whereas AP-2α bound to a more upstream promoter region (-103/-71). Thus, the synergistic activation of the human AM gene promoter by Sp1 and AP-2α may be mediated by the binding of Sp1 to the promoter region (-70/-29) and the interaction with AP-2α, which binds to the promoter region (-103/-71).

Original languageEnglish
Pages (from-to)465-472
Number of pages8
JournalPeptides
Volume29
Issue number3
DOIs
Publication statusPublished - 2008 Mar

Keywords

  • AP-2
  • Adrenomedullin
  • Sp1
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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