Fig. 1

Mechanisms of HIF-1α protein stabilization in hypoxia and degradation in normoxia. a Under normal oxygen tension, HIF-α subunits are expressed, hydroxylated by a family of oxygen dependent prolyl hydroxylases (PHDs), recognised by the von-Hippel Lindau tumor suppressor (pVHL) which leads to HIF-α poly-ubiquitination and subsequent degradation by the 26S proteasome. b Under hypoxic conditions HIF-α is no longer hydroxylated but it dimerizes with the constitutively expressed HIF-β, enters the nucleus and binds to HREs to upregulate transcription of a group of hypoxic responsive genes. c Extensive modifications in chromatin structure, both HIF dependent and independent, also promote gene silencing