Suppression of the hypoxia inducible factor-1 function by redistributing the aryl hydrocarbon receptor nuclear translocator from nucleus to cytoplasm.

ABSTRACT: The aryl hydrocarbon receptor nuclear translocator (ARNT) heterodimerizes with hypoxia inducible factor-1? (HIF-1?), followed by upregulation of genes that are essential for carcinogenesis. We utilized a novel peptide (Ainp1) to address whether the HIF-1? signaling could be suppressed by an ARNT-mediated mechanism. Ainp1 suppresses the HIF-1?-dependent luciferase expression in Hep3B cells and this suppression can be reversed by ARNT. Ainp1 reduces the interaction between ARNT and HIF-1?, 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.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC3319868 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature