Schizosaccharomyces pombe cells lacking the Ran-binding protein Hba1 show a multidrug resistance phenotype due to constitutive nuclear accumulation of Pap1
Schizosaccharomyces pombe cells lacking the Ran-binding protein Hba1 show a multidrug resistance phenotype due to constitutive nuclear accumulation of Pap1
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DOI：
10.1074/jbc.m305859200
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发表时间：
2003-10-17
影响因子：
4.8
通讯作者：
Hidalgo, E
中科院分区：
文献类型：
--
作者：
Castillo, EA;Vivancos, AP;Hidalgo, E
在裂糖酵母（Schizosaccharomyces pombe）中，转录因子Pap1和丝裂原激活蛋白激酶Sty1在非胁迫条件下以依赖于crm1的方式被排除在细胞核外。在氧化处理后，Sty1和Pap1都集中到细胞核中，这是由于进口增强或出口受损。Hba1是一种蛋白质，当过度表达时赋予brefeldin a抗性，它包含Ran结合域。本项目旨在从分子水平上了解Hba1在pombe氧化应激反应中的作用。荧光和共聚焦显微镜研究表明，Hba1位于核质而不是核膜。我们还证明，hba1基因的多拷贝或缺失都会诱导细胞核中Pap1和Sty1的积累。我们提出Hba1协助Crm1输出一些核输出信号蛋白。Pap1核积累足以构成激活其特异性抗氧化反应。相反，在没有胁迫的情况下，Deltahba1菌株中Sty1的本构性核定位不会触发Sty1特异性的、依赖于atf1的抗氧化反应。我们得出结论，缺乏或过表达Hba1的菌株的多药耐药性增加是由于非应激条件下细胞核中Pap1的积累。
In Schizosaccharomyces pombe, the transcription factor Pap1, and the mitogen-activated protein kinase Sty1 are excluded from the nucleus in a Crm1-dependent manner under non-stressed conditions. Upon oxidant treatment, both Sty1 and Pap1 concentrate into the nucleus, due to an enhanced import or an impaired export. Hba1, a protein that when overexpressed confers brefeldin A resistance, contains a Ran binding domain. The purpose of this project was to understand at the molecular level the role of Hba1 in the S. pombe oxidative stress response. Fluorescent and confocal microscopy studies demonstrate that Hba1 is located at the nucleoplasm and not at the nuclear envelope. We also demonstrate that either multiple copies or deletion of the hba1 gene induces nuclear accumulation of Pap1 and Sty1. We propose that Hba1 assists Crm1 to export some nuclear export signal-containing proteins. Pap1 nuclear accumulation is sufficient for constitutive activation of its specific antioxidant response. On the contrary, constitutive nuclear localization of Sty1 in the Deltahba1 strain does not trigger the Sty1-specific, Atf1-dependent antioxidant response in the absence of stress. We conclude that the increased multidrug resistance of strains lacking or overexpressing Hba1 is due to the accumulation of Pap1 in the nucleus under non-stressed conditions.