HIFα targeted for VHL-mediated destruction by proline hydroxylation:: Implications for O2 sensing
HIFα targeted for VHL-mediated destruction by proline hydroxylation:: Implications for O2 sensing
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DOI：
10.1126/science.1059817
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发表时间：
2001-04-20
期刊：
影响因子：
56.9
通讯作者：
Kaelin, WG
中科院分区：
文献类型：
--
作者：
Ivan, M;Kondo, K;Kaelin, WG
缺氧诱导因子（hypoxia-inducible factor，HIF）是一种转录因子，在细胞适应氧可用性变化中起关键作用。在氧存在下，HIF被含有von Hippel-lindau肿瘤抑制蛋白（pVHL）的E3泛素连接酶靶向破坏。我们发现，人pVHL结合到一个短的HIF衍生肽时，保守的脯氨酸残基在这个肽的核心是羟基化。由于脯氨酸羟基化需要分子氧和Fe 2+，这种蛋白质修饰可能在哺乳动物氧传感中起关键作用。
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.