Hypoxia-inducible factor 1 (HIF1) is a heterodimeric transcription factor that plays a critical role in the
cellular response of hypoxia (1). The HIF1 complex
consists of two subunits, HIF1-Alpha and HIF1-Beta,
which are basic helix-loop-helix proteins of the PAS
family (2). HIF1 regulates the transcription of a broad
range of genes that facilitate responses to the hypoxic
environment, including genes regulating angiogenesis,
erythropoiesis, cell cycle, metabolism and apoptosis. The
widely expressed HIF-1α is typically degraded rapidly in
normoxic cells by the ubiquitin/proteasomal pathway.
Under normoxic conditions, HIF-1α is proline
hydroxylated leading to a conformational change that
promotes binding to the von Hippel Lindau protein (VLH)
E3 ligase complex; ubiquitination and proteasomal
degradation follows (3, 4). Both hypoxic conditions and
chemical hydroxylase inhibitors (such as desferrioxamine
and cobalt) inhibit HIF-1α degradation and lead to its
stabilization. In addition, HIF-1α can be induced in an
oxygen-independent manner by various cytokines through
the PI3K-AKT-mTOR pathway (5-7).