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The aryl hydrocarbon receptor nuclear translocator‐interacting peptide 1 suppresses hypoxia inducible factor‐1 alpha signaling via an Arnt‐dependent mechanism
Author(s) -
Wang Yu,
Li Yanjie,
Peng Depeng,
Chan William K
Publication year - 2011
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.25.1_supplement.1007.5
Subject(s) - aryl hydrocarbon receptor nuclear translocator , hypoxia inducible factor 1 , hypoxia inducible factors , aryl hydrocarbon receptor , chemistry , enhancer , cytoplasm , transcription factor , pas domain , microbiology and biotechnology , biology , biochemistry , gene
The aryl hydrocarbon receptor nuclear translocator (Arnt) is a basic‐helix‐loop‐helix‐PAS protein which dimerizes with hypoxia inducible factor‐1α (HIF‐1α) under hypoxia in solid tumors. Hypoxia causes HIF‐1α protein accumulation; binding of the HIF‐1α::Arnt heterodimer to the corresponding enhancers upregulates the expression of genes that are involved in carcinogenesis and angiogenesis. Our objective is to explore whether interference of the Arnt function would suppress the HIF‐1α signaling. We utilized a novel peptide called Arnt‐interacting peptide 1 (Ainp1, 58 amino acids in length), which we had discovered from phage display screening, to address whether the HIF‐1α signaling could be suppressed by an Arnt‐mediated mechanism. Ainp1 suppressed the cobalt chloride‐dependent, HRE‐driven luciferase expression in Hep3B cells in a dose‐dependent manner. Ainp1 did not appear to bind HIF‐1α directly; however, it suppressed the interaction between Arnt and HIF‐1α. The GFP fusion of Ainp1 was located at both the cytoplasm and the nucleus of Hep3B cells. This GFP‐Ainp1 fusion suppressed the CoCl 2 ‐dependent recruitment of Arnt to a HRE‐responsive promoter and decreased the nuclear Arnt content, but not the total Arnt content in Hep3B cells. We concluded that Ainp1 suppresses the HIF‐1α function by reducing the nuclear Arnt content. This work is supported by NIH (WKC, R01ES014050).