Mammalian oxygen sensing, signalling and gene regulation

Oxygen is essential to the life of all aerobic organisms. Virtually every c ell type is able to sense a limited oxygen supply (hypoxia) and specificall y to induce a set of oxygen-regulated genes. This review summarizes current concepts of mammalian oxygen-sensing and signal-transduction pathways. Sin ce the discovery of the hypoxia-inducible factors (HIFs), a great deal of p rogress has been made in our comprehension of how hypoxia induces the expre ssion of oxygen-regulated genes. The alpha subunit of the heterodimeric tra nscription factors HPF-1, 2 and 3 the is unstable under normoxia but is rap idly stabilized upon exposure to hypoxic conditions. Following heterodimeri zation with the constitutively expressed beta subunit, HIFs activate the tr anscription of an increasing number of genes involved in maintaining oxygen homeostasis at the cellular, local and systemic levels.