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F29, a 16‐mer peptide enhances HIF‐1α function
Author(s) -
Mi Choi Su,
Hyunsung Park
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb89-b
Subject(s) - transactivation , peptide , reporter gene , function (biology) , microbiology and biotechnology , chemistry , biology , gene , biochemistry , transcription factor , gene expression
Hypoxia‐inducible factor‐1α is a master regulator of the transcriptional response to oxygen deprivation. HIF‐1α can attenuate ischemic injury by inducing many genes for survival. We screened HIF‐1α‐interacting peptides by using the GAL4‐based yeast two‐hybrid system and a random peptide library. This putative HIF‐1α‐interacting peptide can be a lead compound for HIF‐1α‐specific drugs. Among potential HIF‐1α‐interacting peptides, specifically F29 was tested for its ability to modulate HIF‐1α function. We cloned this 16‐mer peptide into a plasmid (pF29) or synthesized this sequence as a HIV TAT domain containing peptide (TAT‐F29). In vitro interaction assay indicated that F29 interacts with HIF‐1α. Both pF29 and TAT‐F29 increase the hypoxia‐responsive element (HRE)‐driven reporter expression and hypoxia‐induced transactivation ability of HIF‐1α. Furthermore, TAT‐F29 increases the level of HIF‐1α protein and its target genes VEGF and PGK‐1 mRNA in normoxic cells. Taken together, these results indicated that F29 can be an effective lead compound to enhance HIF‐1α function. [Supported by a grant (CBM‐01‐B‐1‐3) from the Center for Biological Modulators of the 21st Century Frontier R&D Program, the Ministry of Science and Technology]