对Pho85细胞周期蛋白依赖性激酶的化学抑制揭示了其在环境应激反应中的作用。
Chemical inhibition of the Pho85 cyclin-dependent kinase reveals a role in the environmental stress response.
作者信息
Carroll A S, Bishop A C, DeRisi J L, Shokat K M, O'Shea E K
机构信息
Howard Hughes Medical Institute, and Departments of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
出版信息
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12578-83. doi: 10.1073/pnas.211195798.
In addition to its well-established role in responding to phosphate starvation, the cyclin-dependent kinase Pho85 has been implicated in a number of other physiological responses of the budding yeast Saccharomyces cerevisiae, including synthesis of glycogen. To comprehensively characterize the range of Pho85-dependent gene expression, we used a chemical genetic approach that enabled us to control Pho85 kinase activity with a cell-permeable inhibitor and whole genome transcript profiling. We found significant phenotypic differences between the rapid loss of activity caused by inhibition and the deletion of the genomic copy of PHO85. We demonstrate that Pho85 controls the expression of not only previously identified glycogen synthetic genes, but also a significant regulon of genes involved in the cellular response to environmental stress. In addition, we show that the effects of this inhibitor are both rapid and reversible, making it well suited to the study of the behavior of dynamic signaling pathways.
除了在应对磷酸盐饥饿方面已确立的作用外，细胞周期蛋白依赖性激酶Pho85还参与了酿酒酵母的许多其他生理反应，包括糖原的合成。为了全面表征Pho85依赖性基因表达的范围，我们采用了一种化学遗传学方法，该方法使我们能够使用细胞可渗透抑制剂和全基因组转录谱来控制Pho85激酶活性。我们发现抑制导致的活性快速丧失与PHO85基因组拷贝缺失之间存在显著的表型差异。我们证明，Pho85不仅控制先前鉴定的糖原合成基因的表达，还控制参与细胞对环境应激反应的大量基因调控子。此外，我们表明这种抑制剂的作用是快速且可逆的，非常适合研究动态信号通路的行为。
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