Peroxiredoxin Ahp1 Acts as a Receptor for Alkylhydroperoxides to Induce Disulfide Bond Formation in the Cad1 Transcription Factor
Peroxiredoxin Ahp1 Acts as a Receptor for Alkylhydroperoxides to Induce Disulfide Bond Formation in the Cad1 Transcription Factor
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DOI：
10.1074/jbc.m109.090142
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发表时间：
2010-04-02
影响因子：
4.8
通讯作者：
Kuge, Shusuke
中科院分区：
文献类型：
--
作者：
Iwai, Kenta;Naganuma, Akira;Kuge, Shusuke
细胞代谢过程中产生的活性氧对细胞具有毒性。因此，细胞必须能够识别ROS作为应激信号，并诱导应激反应途径，保护细胞免受ROS毒性。最近，过氧化物氧还蛋白（Prx）诱导的继电器的二硫键形成已被确定在芽殖酵母，即二硫键形成的Yap 1，氧化应激反应的关键转录因子，由一个特定的Prx Gpx3和一个主要的Prx Tsa1。在这里，我们表明，一个神经元型Prx Ahp1可以作为烷基氢过氧化物的受体，导致激活的Cad1转录因子是同源的Yap1。我们证明，Ahp1是所需的分子间Cad1二硫键（S）在体外氧化还原系统和烷基氢过氧化物处理的细胞中的形成。此外，我们发现，Cad1依赖的HSP 82基因的转录激活依赖于Ahp 1。我们的研究结果表明，虽然Gpx3-Yap1途径比AHP1-Cad1途径更强烈地有助于抵抗，但AHP1诱导的Cad1激活可以作为防御系统对抗由烷基氢过氧化物（可能包括脂质过氧化物）诱导的应激。因此，蛋白质的Prx家族在确定过氧化物反应信号和通过诱导二硫键形成将信号传递到特定靶蛋白中具有重要作用。
Reactive oxygen species (ROS) generated during cellular metabolism are toxic to cells. As a result, cells must be able to identify ROS as a stress signal and induce stress response pathways that protect cells from ROS toxicity. Recently, peroxiredoxin (Prx)-induced relays of disulfide bond formation have been identified in budding yeast, namely the disulfide bond formation of Yap1, a crucial transcription factor for oxidative stress response, by a specific Prx Gpx3 and by a major Prx Tsa1. Here, we show that an atypical-type Prx Ahp1 can act as a receptor for alkylhydroperoxides, resulting in activation of the Cad1 transcription factor that is homologous to Yap1. We demonstrate that Ahp1 is required for the formation of intermolecular Cad1 disulfide bond(s) in both an in vitro redox system and in cells treated with alkylhydroperoxide. Furthermore, we found that Cad1-dependent transcriptional activation of the HSP82 gene is dependent on Ahp1. Our results suggest that, although the Gpx3-Yap1 pathway contributes more strongly to resistance than the Ahp1-Cad1 pathway, the Ahp1-induced activation of Cad1 can function as a defense system against stress induced by alkylhydroperoxides, possibly including lipid peroxides. Thus, the Prx family of proteins have an important role in determining peroxide response signals and in transmitting the signals to specific target proteins by inducing disulfide bond formation.