UNASSIGNED: @entity519 -inducible transcription factors (HIFs) regulate hundreds of genes involved in cellular adaptation to reduced @entity26 availability. HIFs consist of an @entity3612 -labile a-subunit (primarily @entity7738 and @entity2032 ) and a constitutive HIF-1b subunit. In normoxia the HIF-a subunit is hydroxylated by members of a family of @entity10783 -4-hydroxylase domain (PHD) proteins, PHD1-3, resulting in recognition by @entity280 protein, ubiquitination and proteasomal degradation. In contrast, reduced @entity26 availability inhibits PHD activity resulting in @entity7738 stabilisation and nuclear accumulation. Nuclear import of @entity7738 mainly depends on classical @entity7303 ( @entity7303 ) and involves importin a/b heterodimers. Recently, a specific inhibitor of nuclear import has been identified that inhibits importin a/b-dependent import with no effects on a range of other nuclear transport pathways involving members of the importin protein family. In this study we evaluated the physiological activity of this importin a/b-inhibitor ( @entity3070 ) in the @entity519 response pathway. Treatment with @entity3070 decreases binding activity of @entity7738 to the importin a/b-heterodimer. Moreover, @entity7738 nuclear localisation, nuclear @entity7738 protein levels, HIF-target gene expression, as well as HIF-transcriptional activity are reduced upon @entity3070 treatment. For the first time, we demonstrate the effect of specific importin a/b-inhibition on the @entity519 response on the molecular level.

The importin a/b-specific inhibitor @entity3070 affects HIF-dependent XXXX response pathways.

@entity3070 :: ('MESH:D007559', 'Chemical') :: ['Ivermectin'] @entity7738 :: ('3091', 'Gene') :: ['HIF-1a'] @entity7303 :: ('MESH:C566796', 'Disease') :: ['nuclear localisation signals', 'NLS'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity2032 :: ('2034', 'Gene') :: ['HIF-2a'] @entity519 :: ('MESH:D000860', 'Disease') :: ['Hypoxia', 'hypoxic', 'hypoxia'] @entity3612 :: ('D013481', 'Chemical') :: ['O2'] @entity10783 :: ('CHEBI:26274', 'Chemical') :: ['prolyl'] @entity280 :: ('MESH:D006623', 'Disease') :: ['von Hippel-Lindau']
@entity519 :: (MESH:D000860,Disease) :: ['hypoxia']
