How to catch a HIF—the work of Gregg Semenza`s lab on hypoxia-inducible factor 1 [Protein Synthesis and Degradation] (Journal of Biological Chemistry)

Molecular oxygen is essential for the viability and function of every cell of the animal body. Because skin, tissues, and organs impede oxygen diffusion directly from the air, molecular oxygen concentrations inside the body often are less than 5% (1), much lower than the 21% in Earth`s atmosphere.As multicellular organisms evolved, this steep oxygen gradient necessitated the development of structures such as the circulatory system and of biochemical mechanisms that monitor and control oxygen levels in the body.A major player in sensing potentially harmful drops in cellular oxygen concentrations (hypoxia) is the transcription factor hypoxia-inducible factor 1 (HIF-1).2 HIF-1, and its close relative HIF-2, regulate many genes, including the erythropoietin (EPO) gene, which encodes a hormone that stimulates production of red blood cells (2, 3).One important milestone in uncovering HIF-1`s pivotal role in oxygen sensing was its purification and biochemical characterization in the mid-1990s by the lab of Gregg Semenza (Fig. 1), a geneticist at Johns Hopkins University School of Medicine. This work was reported in two JBC papers recognized as Classics here (4, 5).jbc;295/3/715/F1F1F1Figure 1.Gregg Semenza and colleagues isolated and biochemically characterized the HIF-1 protein. Photo courtesy of Johns Hopkins Medicine.`JBC was the first choice,` says Semenza, referring to the publication of the first Classics article. `To me, that was a classic JBC paper.`A few years before this work, Semenza`s team had found that hypoxia induces the binding of a nuclear protein to a 50-nucleotide-long enhancer region located in the 3´-flanking region of the EPO gene (2, 3). Although...