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Molecular oxygen (O2) is essential for mammalian metabolic processes such as oxidative phosphorylation. Thus, survival depends upon instantaneous transcriptional modulation of genes that maintain O2 homeostasis. Transcriptional control of several of these genes is mediated by hypoxia-inducible factor 1 (HIF-1). HIF-1 is a heterodimer whose α and β subunits are members of the PAS family of basic helix-loop-helix (bHLH) transcription factors. Common structural features of these proteins are an N-terminal bHLH DNA-binding domain and multiple PAS domains that confer dimerization ability and target gene specificity. Members diverge in their C-terminal regions. HIF-1β is also known as the arylhydrocarbon nuclear translocator which is part of the functional dioxin receptor. However, HIF-1α functions exclusively to mediate responses to O2 deprivation. It contains C-terminal and internal transactivation domains. Although HIF-1 aproteinlevels increase during hypoxia, it is unstable in the presence of O2 due to an oxygen-dependent degradation domain (ODD) that targets it for ubiquitination. Thus, HIF-1α is essential for functional HIF-1 to mediate gene transcription in response to hypoxia.Immunofluorescence, Western Blotting
