Nutrient signaling through TOR kinases controls gene expression and cellular differentiation in fungi.
Nutrient signaling through TOR kinases controls gene expression and cellular differentiation in fungi.
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DOI：
10.1007/978-3-642-18930-2_4
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发表时间：
2004
影响因子：
--
通讯作者：
John Rohde;M. Cárdenas
中科院分区：
文献类型：
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作者：
John Rohde;M. Cárdenas
TOR激酶首先在酵母中被鉴定为免疫抑制药物雷帕霉素的靶点。随后使用雷帕霉素作为酵母工具的研究使我们深入了解了TOR激酶的结构和功能，以及TOR信号传导程序在传递营养信号以促进细胞生长方面的生物学作用。该领域的主要进展之一是确定了TOR信号在转录调控中的意想不到的作用。受TOR调节的靶基因的鉴定为TOR激酶下游的信号传导事件的解剖提供了平台。旨在理解TOR调节转录的研究已经开始阐明TOR信号如何与其他信号程序合作。此外，TOR途径与高度保守的MAP激酶和PKA信号传导程序一起调节假菌丝分化的发育程序。值得注意的是，雷帕霉素还阻断了许多重要的人类和植物病原体的抑制作用，并且雷帕霉素的作用机制在白色念珠菌和新型隐球菌中是保守的。雷帕霉素的免疫抑制性较低的类似物的抗微生物特性为开发有效的抗真菌治疗提供了希望。
The TOR kinases were first identified inSaccharomyces cerevisiaeas the targets of the immunosuppressive drug rapamycin. Subsequent studies employing rapamycin as a tool in yeast have given us insight into the structure and function of the TOR kinases, as well as the biological role of the TOR signaling program in transmitting nutrient signals to promote cell growth. One of the major advances from this area has been in defining an unexpected role for TOR signaling in the regulation of transcription. The identification of target genes subject to regulation by TOR has provided a platform for the dissection of the signaling events downstream of the TOR kinases. Studies aimed at understanding TOR-regulated transcription have begun to shed light on how TOR signaling cooperates with other signaling programs. In addition, the TOR pathway regulates the developmental program of pseudohyphal differentiation in concert with highly conserved MAP kinase and PKA signaling programs. Remarkably, rapamycin also blocks filamentation in a number of important human and plant pathogens and the mechanism of rapamycin action is conserved inCandida albicansandCryptococcus neoformans. The antimicrobial properties of less immunosuppressive analogs of rapamycin hold promise for the development of an effective antifungal therapy.