Hypoxia regulation of gene transcription

Abstract

The adaptive responses to hypoxia include the transcriptional activation of various genes like those encoding for glycolytic enzymes, growth factors and vasoactive peptides that tend to ameliorate the damaging effect of the lack of oxygen. Most of these genes are regulated by the hypoxia-inducible factor 1 complex (HIF-1), a heterodimer protein complex that activates transcription through binding to specific hypoxic-responsive sequences (HRE) present in those genes. Hypoxia induces HIF-1 complex formation by stabilizing the HIF-1alpha sub-unit, which under normoxic conditions is degraded by the ubiquitin-proteasome system. The molecular mechanisms by which cells sense the hypoxic signal and transduce the hypoxic response are still not clear. The more accepted models for oxygen sensing involve the participation of heme-proteins sensors or are based in redox-reactions which may or not involve participation of mitochondria.