HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O <sub>2</sub> Sensing
Mircea Ivan(Brigham and Women's Hospital), Keiichi Kondo(Brigham and Women's Hospital), Haifeng Yang(Brigham and Women's Hospital), William Kim(Brigham and Women's Hospital), Jennifer Valiando(Brigham and Women's Hospital), Michael Ohh(Brigham and Women's Hospital), Adrian Salic(Harvard University), John M. Asara(Harvard University), William S. Lane(Harvard University), William G. Kaelin(Brigham and Women's Hospital)
Cited by 4,687Open Access
Abstract
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.
Related Papers
No related papers found
Powered by citation graph analysis