RT Journal Article
SR Electronic
T1 HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O<sub>2</sub> 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.