Modulation of fungal sensitivity to staurosporine by targeting proteins identified by transcriptional profiling.
Modulation of fungal sensitivity to staurosporine by targeting proteins identified by transcriptional profiling.
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DOI：
10.1016/j.fgb.2011.09.004
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发表时间：
2011-12
影响因子：
3
通讯作者：
Videira, Arnaldo
中科院分区：
文献类型：
--
作者：
Fernandes, Andreia S.;Pedro Goncalves, A.;Castro, Ana;Lopes, Telma A.;Gardner, Rui;Glass, N. Louise;Videira, Arnaldo
通过转录谱分析粗糙脉孢菌对死亡诱导剂星形孢菌素的时间依赖性遗传反应。星形孢菌素诱导了编码 ABC 转运蛋白和与钾通道调节亚基相似的蛋白质的两个主要基因。转录反应取决于新转录因子的活性。差异表达基因中的缺失突变体显示出对十字孢菌素的敏感性改变，强调了参与药物反应的重要蛋白质。 ABC转运蛋白的无效突变体(abc3)对星形孢菌素极其敏感，比野生型菌株积累更多的星形孢菌素，并且在能量依赖性药物输出方面存在缺陷，表明ABC3蛋白是第一个被描述的星形孢菌素转运蛋白。通过免疫荧光显微镜将其定位于质膜中。 ABC转运蛋白或钾通道抑制剂与星形孢菌素的组合可增强对抗粗糙脉孢菌和病原真菌的活性，为开发更有效和更特异性的抗真菌药物铺平道路。我们的结果强调了转录分析在鉴定参与细胞死亡的新型蛋白质及其作为药物靶点的潜在用途方面的一般用途。
An analysis of the time-dependent genetic response to the death-inducer staurosporine was performed in Neurospora crassa by transcriptional profiling. Staurosporine induced two major genes encoding an ABC transporter and a protein with similarity to regulatory subunits of potassium channels. The transcriptional response is dependent on the activity of a novel transcription factor. Deletion mutants in differentially expressed genes displayed altered sensitivity to staurosporine, underscoring significant proteins involved in the response to the drug. A null-mutant of the ABC transporter (abc3) is extremely sensitive to staurosporine, accumulates more staurosporine than the wild type strain and is defective in energy-dependent export of the drug, indicating that the ABC3 protein is the first described staurosporine transporter. It was located in the plasma membrane by immunofluorescence microscopy. The combination of inhibitors of ABC transporters or of potassium channels with staurosporine leads to an enhanced activity against N. crassa and pathogenic fungi paving the way to the development of more potent and specific antifungals. Our results highlight the general use of transcriptional profiling for the identification of novel proteins involved in cell death and their potential use as drug targets.
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影响因子：
14.9
作者：
Ren Q;Chen K;Paulsen IT
通讯作者：
Paulsen IT
粗糙脉孢菌中的长寡聚体微阵列分析揭示了分生孢子萌发的生化和生理事件背后的转录程序。
影响因子：
14.9
作者：
Kasuga, T;Townsend, JP;Tian, CG;Gilbert, LB;Mannhaupt, G;Taylor, JW;Glass, NL
通讯作者：
Glass, NL
DOI：
10.1126/science.1168750
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Aller SG;Yu J;Ward A;Weng Y;Chittaboina S;Zhuo R;Harrell PM;Trinh YT;Zhang Q;Urbatsch IL;Chang G
通讯作者：
Chang G
影响因子：
4.9
作者：
Nascimento, AM;Goldman, GH;Perlin, DS
通讯作者：
Perlin, DS
影响因子：
3.3
作者：
OMURA, S;IWAI, Y;MASUMA, R
通讯作者：
MASUMA, R