Prolyl hydroxylase domain protein 3 targets Pax2 for destruction.
Prolyl hydroxylase domain protein 3 targets Pax2 for destruction.
复制标题
脯氨酰羟化酶结构域蛋白 3 以 Pax2 为目标进行破坏。
DOI：
10.1016/j.bbrc.2011.05.012
复制
发表时间：
2011-06
影响因子：
3.1
通讯作者：
中科院分区：
文献类型：
--
作者：
脯氨酸羟基酶结构域蛋白(PhDS)在有氧条件下使缺氧诱导因子α羟化，导致缺氧诱导因子α蛋白酶体破坏。PHD家族包括PHD-1、PHD-2和PHD-3。最近的研究表明，除了HIF-α，PHD还有其他底物。Pair box(Pax)2是一种转录因子，在多种肿瘤中均有异常表达。然而，潜在的机制仍不清楚。在这里，我们证明PHD3是Pax2表达的负调控因子。我们发现PHD3与Pax2结合并直接介导Pax2的破坏。抑制PHD3羟基酶活性可导致Pax2蛋白表达上调，但不影响其基因表达水平。我们发现，在结直肠癌中，Pax2蛋白表达增加，PHD3蛋白表达降低，且Pax2蛋白表达增加与PHD3蛋白表达降低相关。我们的结果表明，PHD3的目标是Pax2。这一发现可能揭示了癌细胞中Pax2表达的调节机制。
Prolyl hydroxylase domain proteins (PHDs) hydroxylate HIFα in the presence of oxygen, leading to HIFα proteasomal destruction. The PHDs family comprises PHD1, 2, and 3. Recent studies indicate that, in addition to HIFα, PHDs have other substrates. Paired box (Pax) 2, a transcription factor, was found aberrantly expressed in a variety of cancers. However, the underlying mechanisms remain unknown. Here we demonstrate that PHD3 is a negative regulator of expression of Pax2. We found that PHD3 bound to Pax2 and mediated Pax2 destruction directly. Inhibition of PHD3 hydroxylase activity led to upregulation of Pax2 protein but not mRNA level. We found that Pax2 protein was increased and PHD3 protein was decreased in colorectal cancer, and the increased Pax2 was associated with decreased PHD3. Our results suggest that PHD3 targets Pax2 for destruction. The findings may disclose a mechanism for the regulation of Pax2 expression in cancer cells.
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影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
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影响因子：
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Xie L;Xiao K;Whalen EJ;Forrester MT;Freeman RS;Fong G;Gygi SP;Lefkowitz RJ;Stamler JS
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通讯作者：
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通讯作者：
Schlisio, S
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