How HIF-1α Handles Stress

A transcription factor responds to low oxygen by controlling gene expression, DNA replication, and cell division to promote survival. Metazoans cope with hypoxia—oxygen deficiency in the tissues—by eliciting elaborate cellular responses to balance oxygen supply and demand. At the molecular level, adaptation relies primarily on the hypoxia-inducible factor 1α (HIF-1α), a transcription factor, and its binding partner ARNT (also called HIF-1β). This complex activates numerous target genes to limit oxygen consumption and push the cell into survival mode ( 1 ). The scope of HIF-1α action is expanding, though, as it seems to have nontranscriptional activities that reduce DNA replication and slow down cell proliferation when oxygen becomes scarce (see the figure).