HIFα targeted for VHL-mediated destruction by proline hydroxylation:: Implications for O2 sensing

被引：3888

作者：

Ivan, M

Kondo, K

Yang, HF

Kim, W

Valiando, J

Ohh, M

Salic, A

Asara, JM

Lane, WS

Kaelin, WG

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[5] Harvard Univ, Microchem & Proteom Anal Facil, Cambridge, MA 02138 USA

来源：

SCIENCE | 2001年 / 292卷 / 5516期

关键词：

D O I：

10.1126/science.1059817

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：464 / 468

页数：5

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