Hypoxia-dependent sequestration of an oxygen sensor by a widespread structural motif can shape the hypoxic response--a predictive kinetic model.

ABSTRACT:

Background

The activity of the heterodimeric transcription factor hypoxia inducible factor (HIF) is regulated by the post-translational, oxygen-dependent hydroxylation of its α-subunit by members of the prolyl hydroxylase domain (PHD or EGLN)-family and by factor inhibiting HIF (FIH). PHD-dependent hydroxylation targets HIFα for rapid proteasomal degradation; FIH-catalysed asparaginyl-hydroxylation of the C-terminal transactivation domain (CAD) of HIFα suppresses the CAD-dependent subset of the extensive transcriptional responses induced by HIF. FIH can also hydroxylate ankyrin-repeat domain (ARD) proteins, a large group of proteins which are functionally unrelated but share common structural features. Competition by ARD proteins for FIH is hypothesised to affect FIH activity towar

SUBMITTER: Schmierer B 

PROVIDER: S-EPMC2984394 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature