Drugging the undruggables: exploring the ubiquitin system for drug development.
Drugging the undruggables: exploring the ubiquitin system for drug development.
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DOI：
10.1038/cr.2016.31
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发表时间：
2016-04
期刊：
影响因子：
44.1
通讯作者：
Dixit VM
中科院分区：
文献类型：
--
作者：
Huang X;Dixit VM
蛋白质水平的动态调节响应于生理线索而受到严格控制。在哺乳动物细胞中，大部分蛋白质降解是由泛素-蛋白酶体系统（UPS）进行的。与激酶类似，泛素系统的组分通常失调，导致各种疾病，包括癌症和神经变性，使其成为有吸引力的药物靶点。然而，到目前为止，只有少数靶向泛素系统的药物获得了FDA的批准。在这里，我们回顾了泛素系统中可能的治疗干预节点，分析了挑战，并强调了最有前途的策略，以针对UPS。
Dynamic modulation of protein levels is tightly controlled in response to physiological cues. In mammalian cells, much of the protein degradation is carried out by the ubiquitin-proteasome system (UPS). Similar to kinases, components of the ubiquitin system are often dysregulated, leading to a variety of diseases, including cancer and neurodegeneration, making them attractive drug targets. However, so far there are only a handful of drugs targeting the ubiquitin system that have been approved by the FDA. Here, we review possible therapeutic intervention nodes in the ubiquitin system, analyze the challenges, and highlight the most promising strategies to target the UPS.