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首页> 外文期刊>Cell metabolism >Activation of the HIF prolyl hydroxylase by the iron chaperones PCBP1 and PCBP2.
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Activation of the HIF prolyl hydroxylase by the iron chaperones PCBP1 and PCBP2.

机译：铁伴侣PCBP1和PCBP2激活HIF脯氨酰羟化酶。

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Mammalian cells express dozens of iron-containing proteins, yet little is known about the mechanism of metal ligand incorporation. Human poly (rC) binding protein 1 (PCBP1) is an iron chaperone that binds iron and delivers it to ferritin, a cytosolic iron storage protein. We have identified the iron-dependent prolyl hydroxylases (PHDs) and asparaginyl hydroxylase (FIH1) that modify hypoxia-inducible factor alpha (HIFalpha) as targets of PCBP1. Depletion of PCBP1 or PCBP2 in cells led to loss of PHD activity, manifested by reduced prolyl hydroxylation of HIF1alpha, impaired degradation of HIF1alpha through the VHL/proteasome pathway, and accumulation of active HIF1 transcription factor. PHD activity was restored in vitro by addition of excess Fe(II), or purified Fe-PCBP1, and PCBP1 bound to PHD2 and FIH1 in vivo. These data indicated that PCBP1 was required for iron incorporation into PHD and suggest a broad role for PCBP1 and 2 in delivering iron to cytosolic nonheme iron enzymes.
机译：哺乳动物细胞表达数十种含铁蛋白，但对金属配体掺入机制知之甚少。人多（rC）结合蛋白1（PCBP1）是一种铁伴侣蛋白，可结合铁并将其传递至铁蛋白，一种胞质铁存储蛋白。我们已经鉴定出铁依赖的脯氨酰羟化酶（PHDs）和天冬酰胺基羟化酶（FIH1）可以将缺氧诱导因子α（HIFalpha）修饰为PCBP1的靶标。细胞中PCBP1或PCBP2的消耗导致PHD活性丧失，表现为HIF1alpha的脯氨酰羟化减少，通过VHL /蛋白酶体途径破坏HIF1alpha的降解以及活性HIF1转录因子的积累。通过在体内添加过量的Fe（II）或纯化的Fe-PCBP1和PCBP1与PHD2和FIH1结合，可恢复PHD活性。这些数据表明PCBP1是铁掺入PHD所必需的，并暗示PCBP1和2在将铁传递至胞质非血红素铁酶中具有广泛的作用。

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