Suppression of the hypoxia inducible factor-1 function by redistributing the aryl hydrocarbon receptor nuclear translocator from nucleus to cytoplasm.
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.
Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, USA.
Yu
Y
Wang
Yanjie
Y
Li
Depeng
D
Wang
Yi
Y
Li
Abraham
A
Chang
William K
WK
Chan
D000595:Amino Acid Sequence; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000378:metabolism*; D008156:Luciferases / Q000037:antagonists & inhibitors / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
C497396:ARNT protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D003035:Cobalt; D008156:Luciferases; C018021:cobaltous chloride