CZT-1 is a novel transcription factor controlling cell death and natural drug resistance in Neurospora crassa.
CZT-1 is a novel transcription factor controlling cell death and natural drug resistance in Neurospora crassa.
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DOI：
10.1534/g3.114.011312
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发表时间：
2014-04-08
期刊：
影响因子：
--
通讯作者：
Videira A
中科院分区：
文献类型：
--
作者：
Gonçalves AP;Hall C;Kowbel DJ;Glass NL;Videira A
我们确定 CZT-1（细胞死亡激活的锌簇转录因子）是一种新型转录因子，参与粗糙脉孢菌中蛋白激酶抑制剂十字孢菌素诱导的细胞死亡耐受。通过RNA测序对星形孢菌素处理的野生型细胞进行转录分析表明，编码蛋白质合成机制的基因在药物抑制的基因中富集。功能类别富集分析还表明，星形孢菌素下调编码线粒体呼吸链成分的基因，而参与内质网活动的基因则上调。相反，星形孢菌素处理的 Δczt-1 缺失菌株无法抑制呼吸链基因并诱导与内质网相关的基因，表明 CZT-1 在调节这些细胞器活性中的作用。 Δczt-1突变株在星形孢菌素损伤后表现出活性氧积累增加。一项针对粗糙猪笼草分离株野生种群的全基因组关联研究指出了与 CZT-1 细胞死亡作用相关的基因，包括过氧化氢酶-1 (cat-1) 和凋亡诱导因子 - 同源线粒体相关死亡诱导剂 2 (amid-2)。重要的是，czt-1 表达的差异与野生分离菌株对十字孢菌素的耐药性相关。我们的结果揭示了一种新的转录因子，它可以调节实验室菌株以及粗糙脉孢菌野生分离株中星形孢菌素的耐药性和细胞死亡。
We pinpoint CZT-1 (cell death–activated zinc cluster transcription factor) as a novel transcription factor involved in tolerance to cell death induced by the protein kinase inhibitor staurosporine in Neurospora crassa. Transcriptional profiling of staurosporine-treated wild-type cells by RNA-sequencing showed that genes encoding the machinery for protein synthesis are enriched among the genes repressed by the drug. Functional category enrichment analyses also show that genes encoding components of the mitochondrial respiratory chain are downregulated by staurosporine, whereas genes involved in endoplasmic reticulum activities are upregulated. In contrast, a staurosporine-treated Δczt-1 deletion strain is unable to repress the genes for the respiratory chain and to induce the genes related to the endoplasmic reticulum, indicating a role for CZT-1 in the regulation of activity of these organelles. The Δczt-1 mutant strain displays increased reactive oxygen species accumulation on insult with staurosporine. A genome-wide association study of a wild population of N. crassa isolates pointed out genes associated with a cell death role of CZT-1, including catalase-1 (cat-1) and apoptosis-inducing factor–homologous mitochondrion-associated inducer of death 2 (amid-2). Importantly, differences in the expression of czt-1 correlates with resistance to staurosporine among wild isolate strains. Our results reveal a novel transcription factor that regulates drug resistance and cell death in response to staurosporine in laboratory strains as well as in wild isolates of N. crassa.
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影响因子：
6.7
作者：
Kretschmer M;Leroch M;Mosbach A;Walker AS;Fillinger S;Mernke D;Schoonbeek HJ;Pradier JM;Leroux P;De Waard MA;Hahn M
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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