Regulation of the fission yeast transcription factor Pap1 by oxidative stress: requirement for the nuclear export factor Crm1 (Exportin) and the stress-activated MAP kinase Sty1/Spc1
Regulation of the fission yeast transcription factor Pap1 by oxidative stress: requirement for the nuclear export factor Crm1 (Exportin) and the stress-activated MAP kinase Sty1/Spc1
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DOI：
10.1101/gad.12.10.1453
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发表时间：
1998-05-15
影响因子：
10.5
通讯作者：
Jones, N
中科院分区：
文献类型：
--
作者：
Toone, WM;Kuge, S;Jones, N
分裂酵母Sty1应激激活的MAP激酶对细胞对各种应激条件的反应至关重要。因此，sty1（-）细胞对营养限制的反应有缺陷，在固定期失去活力，对渗透应激、氧化应激和紫外线处理敏感。其中一些表型是由sty1依赖的Atf1转录因子调控引起的，Atf1转录因子控制减数分裂特异性和渗透应激反应基因。然而，在本报告中，我们证明了细胞对氧化应激和各种细胞毒性药物治疗的反应是Sty1调控Pap1转录因子的结果，Pap1是一种结构和DNA结合与哺乳动物c-Jun蛋白相似的bZip蛋白。我们发现Sty1和Pap1对于参与氧化应激反应的许多基因的表达以及hba2(+)/bfr1（+）和pmd1（+）两个基因的表达都是必需的，这两个基因编码参与多药耐药的能量依赖性转运蛋白。此外，研究表明Pap1受亚细胞定位的应力依赖性变化的调控。在施加氧化应激时，Pap1蛋白依赖于Sty1激酶从细胞质重新定位到细胞核。这种再定位是受调节的蛋白质输出而不是输入的结果，涉及到Crm1（输出蛋白）核输出因子和编码Ran核苷酸交换因子的dcd1(+)/pim1（+）基因。
The fission yeast Sty1 stress-activated MAP kinase is crucial for the cellular response to a variety of stress conditions. Accordingly, sty1(-) cells are defective in their response to nutrient limitation, lose viability in stationary phase, and are hypersensitive to osmotic stress, oxidative stress, and UV treatment. Some of these phenotypes are caused by Sty1-dependent regulation of the Atf1 transcription factor, which controls both meiosis-specific and osmotic stress-responsive genes. However, in this report we demonstrate that the cellular response to oxidative stress and to treatment with a variety of cytotoxic agents is the result of Sty1 regulation of the Pap1 transcription factor, a bZip protein with structural and DNA binding similarities to the mammalian c-Jun protein. We show that both Sty1 and Pap1 are required for the expression of a number of genes involved in the oxidative stress response and for the expression of two genes, hba2(+)/bfr1(+) and pmd1(+), which encode energy-dependent transport proteins involved in multidrug resistance. Furthermore, rye demonstrate that Pap1 is regulated by stress-dependent changes in subcellular localization. On imposition of oxidative stress, the Pap1 protein relocalizes from the cytoplasm to the nucleus in a process that is dependent on the Sty1 kinase. This relocalization is the result of regulated protein export, rather than import, and involves the Crm1 (exportin) nuclear export factor and the dcd1(+)/pim1(+) gene that encodes an Ran nucleotide exchange factor.