Background：Hypoxia-inducible factor 1 （HIF1） is a heterodimeric transcription factor that plays a critical role in the cellular response to hypoxia （1）. The HIF1 complex consists of two subunits, HIF-1a and HIF-1b, which are basic helix-loop-helix proteins of the PAS （Per, ARNT, Sim） 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-1a is typically degraded rapidly in normoxic cells by the ubiquitin/proteasomal pathway. Under normoxic conditions, HIF-1a 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-1a degradation and lead to its stabilization. In addition, HIF-1a can be induced in an oxygen-independent manner by various cytokines through the PI3K-AKT-mTOR pathway （5-7）.HIF-1b is also known as AhR nuclear translocator （ARNT） due to its ability to partner with the aryl hydrocarbon receptor （AhR） to form a heterodimeric transcription factor complex （8）. Together with AhR, HIF-1b plays an important role in xenobiotics metabolism （8）.
