Gangadhar Nidhi M, Stockwell Brent R
Department of Biological Sciences, 614 Fairchild Center, New York, NY 10027, USA.
Curr Opin Chem Biol. 2007 Feb;11(1):83-7. doi: 10.1016/j.cbpa.2006.11.033. Epub 2006 Dec 14.
Chemical genetics has arisen as a tool for the discovery of pathways and proteins in mammalian systems. This approach, comprising small-molecule screening combined with biochemical and genomic target identification methods, enables one to assess which proteins are involved in regulating a particular phenotype. Applied to cell death, this strategy can reveal novel targets and pathways regulating the demise of mammalian cells. Numerous diseases have been linked to the loss of regulation of cell death. Defining the mechanisms governing cell death in these diseases might lead to the discovery of therapeutic agents and targets and provide a richer understanding of the mortality of living systems. Recent advances include the discovery of novel small molecules regulating cell death pathways -- necrostatin and erastin -- as well as the elucidation of the mechanism of death induced in cancer cells by the cytotoxic agent Apratoxin A.
化学遗传学已成为在哺乳动物系统中发现信号通路和蛋白质的一种工具。这种方法包括小分子筛选以及生化和基因组靶点鉴定方法，能让人评估哪些蛋白质参与调节特定表型。应用于细胞死亡研究时，该策略可揭示调节哺乳动物细胞死亡的新靶点和信号通路。许多疾病都与细胞死亡调控缺失有关。明确这些疾病中细胞死亡的调控机制可能会带来治疗药物和靶点的发现，并更深入地理解生命系统的死亡机制。最近的进展包括发现了调节细胞死亡信号通路的新型小分子——坏死素和厄拉斯汀，以及阐明了细胞毒性药物阿普拉毒素A诱导癌细胞死亡的机制。
