Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation.
Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation.
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发表时间：
1997
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通讯作者：
D. Jin;H. Chae;S. Rhee;K. Jeang
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作者：
D. Jin;H. Chae;S. Rhee;K. Jeang
还原-氧化（氧化还原）在NF-κ B活化中起关键作用。不同的刺激似乎利用活性氧（例如过氧化氢）作为激活NF-κ B的常见效应物。抗氧化剂控制细胞内的氧化还原状态，许多这样的分子可以还原H2 O2。然而，在功能上，不同的抗氧化剂对某些转录因子如NF-κ B的氧化还原调节具有不同的选择性。对于NF-κ B，硫氧还蛋白已被描述为比谷胱甘肽或N-乙酰半胱氨酸更有效的抗氧化剂。硫氧还蛋白过氧化物酶是将H2 O2还原连接到硫氧还蛋白的直接酶。已经使用递归序列搜索/与酵母或原核酶的比对鉴定了几种推定的人类硫氧还蛋白过氧化物酶。尚未详细表征细胞内功能。在这里，我们描述了一种新的人类硫氧还蛋白过氧化物酶，抗氧化酶AOE 372，确定凭借其蛋白质-蛋白质相互作用的增殖相关基因，PAG，这也是一个巯基特异性抗氧化剂的产品。在人细胞中，AOE 372定义了一种氧化还原途径，通过调节细胞质中的IkappaB-α磷酸化特异性调节NF-κ B活性。我们发现，AOE 372活性是通过与其他巯基过氧化物酶的同源或异源二聚化来调节的，这意味着亚基分类是调节抗氧化剂特异性的机制。AOE 372功能表明硫氧还蛋白过氧化物酶是H2 O2介导的NF-κ B活化的直接调节剂。
Reduction-oxidation (redox) plays a critical role in NF-kappaB activation. Diverse stimuli appear to utilize reactive oxygen species (e.g. hydrogen peroxide) as common effectors for activating NF-kappaB. Antioxidants govern intracellular redox status, and many such molecules can reduce H2O2. However, functionally, it does appear that different antioxidants are variously selective for redox regulation of certain transcription factors such as NF-kappaB. For NF-kappaB, thioredoxin has been described to be a more potent antioxidant than either glutathione or N-acetylcysteine. Thioredoxin peroxidase is the immediate enzyme that links reduction of H2O2 to thioredoxin. Several putative human thioredoxin peroxidases have been identified using recursive sequence searches/alignments with yeast or prokaryotic enzymes. None has been characterized in detail for intracellular function(s). Here, we describe a new human thioredoxin peroxidase, antioxidant enzyme AOE372, identified by virtue of its protein-protein interaction with the product of a proliferation association gene, pag, which is also a thiol-specific antioxidant. In human cells, AOE372 defines a redox pathway that specifically regulates NF-kappaB activity via a modulation of IkappaB-alpha phosphorylation in the cytoplasm. We show that AOE372 activity is regulated through either homo- or heterodimerization with other thiol peroxidases, implicating subunit assortment as a mechanism for regulating antioxidant specificities. AOE372 function suggests thioredoxin peroxidase as an immediate regulator of H2O2-mediated activation of NF-kappaB.