The novel peptide F29 facilitates the DNA-binding ability of hypoxia-inducible factor-1α

Su Mi Choi, Hyunsung Park

Research output: Contribution to journalArticle

Abstract

Hypoxia-inducible factor-1α/β (HIF-1α/β) is a heterodimeric transcriptional activator that mediates gene expression in response to hypoxia. HIF-1α has been noted as an effective therapeutic target for ischemic diseases such as myocardiac infarction, stroke and cancer. By using a yeast two-hybrid system and a random peptide library, we found a 16-mer peptide named F29 that directly interacts with the bHLH-PAS domain of HIF-1α. We found that F29 facilitates the interaction of the HIF-1α/β heterodimer with its target DNA sequence, hypoxia-responsive element (HRE). The transient transfection of an F29-expressing plasmid increases the expression of both an HRE-driven luciferase gene and the endogenous HIF-1 target gene, vascular endothelial growth factor (VEGF). Taken together, we conclude that F29 increases the DNA-binding ability of HIF-1α, leading to increased expression of its target gene VEGF. Our results suggest that F29 can be a lead compound that directly targets HIF-1α and increases its activity.

Original languageEnglish (US)
Pages (from-to)737-742
Number of pages6
JournalBMB Reports
Volume42
Issue number11
DOIs
StatePublished - Nov 2009

Keywords

  • HIF-1α
  • Hypoxia
  • Peptide library
  • VEGF
  • bHLH-PAS

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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