Siah proteins, HIF prolyl hydroxylases, and the physiological response to hypoxia

New evidence suggests that at least two members of the family of hypoxia-inducible factor (HIF) prolyl hydroxylases that regulate HIF stability in response to oxygen (O2) availability are also targeted for proteosome-dependent degradation by the E3 ubiquitin ligases Siah1a and Siah2. This preview examines cellular responses to O2 deprivation (hypoxia) and the complexity of the regulation of the HIF O2 sensing pathway in mammals.     

The role of HIF in immunity

Oxygen is an essential nutrient for eukaryotic life and in complex organisms a finely tuned system, based on Hypoxia Inducible Factor (HIF), has evolved to control the cellular, local and organism-wide responses to its availability. Cells of the immune system must function in a variety of local environments and it is now clear that oxygen availability is an important signal for the cells involved in immune defence. This review summarises the mechanisms by which activation of the HIF pathway influences, and is influenced by, both immune activation state and oxygen tension. It is likely that understanding how oxygen tension modulates immune function will provide insights into disease pathogenesis, and may offer new opportunities for treatment.