HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing

作者：Mircea Ivan, Keiichi Kondo, Haifeng Yang, William Kim, Jennifer Valiando, Michael Ohh, Adrian Salic, John M. Asara, William S. Lane, William G. Kaelin · 发表于：Science · 年份：2001 · DOI：10.1126/science.1059817 · 被引用次数：4726 · 研究领域：Cancer, Hypoxia, and Metabolism、Metabolism, Diabetes, and Cancer、Fibroblast Growth Factor Research

HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing.