Activation of the redox sensor Pap1 by hydrogen peroxide requires modulation of the intracellular oxidant concentration
Activation of the redox sensor Pap1 by hydrogen peroxide requires modulation of the intracellular oxidant concentration
复制标题
过氧化氢激活氧化还原传感器 Pap1 需要调节细胞内氧化剂浓度
作者：
Ana Vivancos;Esther A. Castillo;N. Jones;J. Ayté;E. Hidalgo
转录因子Pap1和MAP激酶Sty1是裂殖酵母中过氧化氢诱导反应的关键调节因子。Pap1可以在低但不高的过氧化氢浓度下快速激活。MAP激酶Sty1已被报道参与氧化剂对Pap1的激活。在这里，我们提供了生物化学和遗传学证据，证明过氧化氢诱导的Pap1二硫键在体内形成，这先于转录因子的快速和可逆的核积累。我们发现，在氧化损伤之前激活Sty1级联反应，或过表达Sty1调节的基因ctt1（编码过氧化氢酶）或gpx1（编码谷胱甘肽过氧化物酶），即使在高剂量的过氧化氢下也可以加速Pap1进入。事实上，Sty1的缺乏阻碍了Pap1的核定位，但只有在高剂量的氧化剂。我们提出，低剂量的过氧化氢直接导致Pap1氧化激活，而高浓度的氧化剂最初激活Sty1途径，随之而来的是清除酶的增加，这反过来有助于分解过量的过氧化氢，并达到适当的浓度用于随后的Pap1激活。我们的研究结果还表明，在高剂量的过氧化氢的激活Sty1也可能需要触发其他抗氧化活性，如那些恢复半胱氨酸残基的过度氧化在Pap1途径。
The transcription factor Pap1 and the MAP kinase Sty1 are key regulators of hydrogen peroxide‐induced responses in Schizosaccharomyces pombe. Pap1 can be activated quickly at low, but not high, hydrogen peroxide concentrations. The MAP kinase Sty1 has been reported to participate in Pap1 activation by the oxidant. Here, we provide biochemical and genetic evidence for the in vivo formation of a hydrogen peroxide‐induced disulphide bond in Pap1, which precedes the rapid and reversible nuclear accumulation of the transcription factor. We show that activation of the Sty1 cascade before the oxidative insult, or overexpression of the Sty1‐regulated genes ctt1 (encoding catalase) or gpx1 (encoding glutathione peroxidase), can accelerate Pap1 entry even at high doses of hydrogen peroxide. In fact, the lack of Sty1 impedes Pap1 nuclear localization, but only at high doses of the oxidant. We propose that, whereas low doses of hydrogen peroxide lead directly to Pap1 oxidation‐activation, high concentrations of the oxidant initially activate the Sty1 pathway, with the consequent increase in scavenging enzymes, which in turn helps to decompose the excess of hydrogen peroxide and achieve an appropriate concentration for the subsequent activation of Pap1. Our results also suggest that activation of Sty1 at high doses of hydrogen peroxide may also be required to trigger other antioxidant activities such as those reverting the overoxidation of cysteine residues at the Pap1 pathway.
粟酒裂殖酵母中的 Brefeldin A 敏感性和抗性。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Turi,TG;Webster,P;Rose,JK
通讯作者：
Rose,JK