RT Journal Article SR Electronic T1 HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing JF Science JO Science FD American Association for the Advancement of Science SP 464 OP 468 DO 10.1126/science.1059817 VO 292 IS 5516 A1 Ivan, Mircea A1 Kondo, Keiichi A1 Yang, Haifeng A1 Kim, William A1 Valiando, Jennifer A1 Ohh, Michael A1 Salic, Adrian A1 Asara, John M. A1 Lane, William S. A1 Kaelin Jr., William G. YR 2001 UL http://science.sciencemag.org/content/292/5516/464.abstract AB 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 Fe2+, this protein modification may play a key role in mammalian oxygen sensing.