Abstract
The aryl hydrocarbon receptor nuclear translocator (ARNT) heterodimerizes with hypoxia inducible factor-1α (HIF-1α), followed by upregulation of genes that are essential for carcinogenesis. We utilized a novel peptide (Ainp1) to address whether the HIF-1α signaling could be suppressed by an ARNT-mediated mechanism. Ainp1 suppresses the HIF-1α-dependent luciferase expression in Hep3B cells and this suppression can be reversed by ARNT. Ainp1 reduces the interaction between ARNT and HIF-1α, suppresses the formation of the HIF-1 gel shift complex, and suppresses the ARNT recruitment to the vegf promoter. These effects are partly mediated by redistribution of the nuclear ARNT contents to the cytoplasm.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism*
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Base Sequence
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Cell Line, Tumor
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Cell Nucleus / metabolism
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Cobalt / pharmacology
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Cytoplasm / metabolism
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Immunoprecipitation
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Liver Neoplasms / metabolism*
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Luciferases / antagonists & inhibitors
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Luciferases / genetics
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Molecular Sequence Data
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Promoter Regions, Genetic
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Protein Multimerization
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Transfection
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Vascular Endothelial Growth Factor A / genetics
Substances
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ARNT protein, human
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Aryl Hydrocarbon Receptor Nuclear Translocator
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Cobalt
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Luciferases
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cobaltous chloride