The novel peptide F29 facilitates the DNA-binding ability of hypoxia-inducible factor-1alpha.
Hypoxia-inducible factor-1alpha/beta (HIF-1alpha/beta) is a heterodimeric transcriptional activator that mediates gene expression in response to hypoxia. HIF-1alpha 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-1alpha. We found that F29 facilitates the interaction of the HIF-1alpha/beta 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-1alpha, leading to increased expression of its target gene VEGF. Our results suggest that F29 can be a lead compound that directly targets HIF-1alpha and increases its activity.
Choi
Su Mi
SM
Department of Life Science, University of Seoul, Seoul, Korea.
Park
Hyunsung
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D020798:Two-Hybrid System Techniques
D017931:DNA Primers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010455:Peptides; D004247:DNA