Coactivators necessary for transcriptional output of the hypoxia inducible factor, HIF, are directly recruited by ARNT PAS-B.

ABSTRACT: Hypoxia-inducible factor (HIF) is the key transcriptional effector of the hypoxia response in eukaryotes, coordinating the expression of genes involved in oxygen transport, glycolysis, and angiogenesis to promote adaptation to low oxygen levels. HIF is a basic helix-loop-helix (bHLH)-PAS (PER-ARNT-SIM) heterodimer composed of an oxygen-labile HIF-α subunit and a constitutively expressed aryl hydrocarbon receptor nuclear translocator (ARNT) subunit, which dimerize via basic helix-loop-helix and PAS domains, and recruit coactivators via HIF-α C-terminal transactivation domains. Here we demonstrate that the ARNT PAS-B domain provides an additional recruitment site by binding the coactivator transforming acidic coiled-coil 3 (TACC3) in a step necessary for transcriptional responses to hypoxia.

SUBMITTER: Partch CL 

PROVIDER: S-EPMC3093465 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature