One of the most important factors in the cellular response to hypoxia is hypoxiainducible factor (HIF), which transcriptionally activates genes encoding proteins that mediate adaptive responses to reduced oxygen availability. HIF is a heterodimer consisting of one of three subunits (HIF1-a, HIF2-a, or HIF3-a) bound to the aryl hydrocarbon receptor nuclear translocator (ARNT), which is also known as HIF1-ß. HIF-a is a member of the basic helix-loop-helix (bHLH) superfamily, in which the HLH domain mediates subunit dimerization while the basic domain binds to DNA. HIF target genes play critical roles in metabolism, angiogenesis, cell proliferation, and cell survival; in fact, HIF3-a may be a marker for tumor growth and angiogenesis . Examples of HIF target genes include VEGF, glucose transporter 1 (GLUT1), and EPO. HIF binds to the hypoxia-responsive element, which contains the core recognition sequence 5'-TACGTG-3', in the cis-regulatory regions of hypoxiainducible genes. Transcriptional activation by HIF is linked to its ability to recruit coactivator proteins such as CREB-binding protein (CBP), p300, steroid receptor coactivator-1, and translation initiation factor 2. Hif3a may be a marker for tumor growth and angiogenesis.