A biochemical mechanism that cells use to cope with hypoxia (lack of oxygen) actually cooperates with a less well-known mechanism that helps increase the expression of those hypoxia-sensitive genes, according to investigators at St. Jude Children’s Research Hospital. The two mechanisms each enable a transcription factor called hypoxia-inducible factor (HIF) to increase expression of genes that the cell uses to respond to the stress of hypoxia. Transcription factors bind to a site on the gene called the promoter and trigger the process that decodes the gene and makes the protein for which that gene codes. HIF binds to and activates many genes that contribute to the survival response of tumors; for example, genes that control biochemical reactions that don’t require oxygen to extract energy from glucose or genes needed to build new blood vessels that bring additional oxygen to hypoxic cells. The St. Jude finding is important because it suggests that developing new therapies that interfere with both mechanisms instead of just one might enhance the efficacy of treatments designed for solid tumors that become hypoxic as they outgrow their oxygen supply, according to Paul Brindle, Ph.D., an associate member of the Department of Biochemistry. Brindle is senior author of a report on this work that appeared in November 16 issue of The EMBO Journal.
