Two redox centers within Yap1 for H2O2 and thiol-reactive chemicals signaling
Two redox centers within Yap1 for H2O2 and thiol-reactive chemicals signaling
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DOI：
10.1016/s0891-5849(03)00434-9
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发表时间：
2003-10-15
影响因子：
7.4
通讯作者：
Toledano, MB
中科院分区：
文献类型：
--
作者：
Azevedo, D;Tacnet, F;Toledano, MB
Yap 1转录因子调节酵母对H2 O2和几种不相关的化学物质和金属的反应。通过H2 O2激活涉及由H2 O2传感器Orp 1/Gpx 3指导的Yap 1 Cys 303-Cys 598分子内二硫键形成。我们在这里表明，亲电体N-乙基马来酰亚胺激活Yap 1的共价修饰的Yap 1的C-末端Cys 598，Cys 620，和Cys 629，在Orp 1和雅普I-氧化独立的方式，从而建立一个替代和不同的模式的Yap 1激活。我们还表明，甲萘醌，超氧阴离子发生器和高活性亲电试剂，操作两种模式的Yap 1激活。此外，Yap 1 C-末端结构域对其他亲电体（4-羟基壬烯醛，碘乙酰胺）和金属（镉，硒）的反应性表明了一种常见的机制，用于传感硫醇反应性化学品，涉及硫醇化学修饰。我们建议Yap 1有两个不同的分子氧化还原中心，一个由ROS（氢过氧化物和超氧阴离子）触发，另一个由具有硫醇反应性的化学物质（亲电体和二价重金属阳离子）触发。这些数据表明，酵母细胞不能通过相同的分子装置感知这些化合物，尽管它们都是亲电子的。(C)2003年爱思唯尔公司
The Yap1 transcription factor regulates yeast responses to H2O2 and to several unrelated chemicals and metals. Activation by H2O2 involves Yap1 Cys303-Cys598 intra-molecular disulfide bond formation directed by the H2O2 sensor Orp1/Gpx3. We show here that the electrophile N-ethylmaleimide activates Yap1 by covalent modification of Yap1 C-terminal Cys598, Cys620, and Cys629, in an Orp1 and Yap I-oxidation-independent way, thus establishing an alternate and distinct mode of Yap1 activation. We also show that menadione, a superoxide anion generator and a highly reactive electrophile, operates both modes of Yap1 activation. Further, the Yap1 C-terminal domain reactivity towards other electrophiles (4-hydroxynonenal, iodoacetamide) and metals (cadmium, selenium) suggests a common mechanism for sensing thiol reactive chemicals, involving thiol chemical modification. We propose that Yap1 has two distinct molecular redox centers, one triggered by ROS (hydroperoxides and the superoxide anion) and the other by chemicals with thiol reactivity (electrophiles and divalent heavy metals cations). These data indicate that yeast cells cannot sense these compounds through the same molecular devices, albeit they are all electrophilic. (C) 2003 Elsevier Inc.