The ubiquitin proteasome system (UPS) is one of the main proteolytic pathways in eukaryotic cells, playing an essential role in key cellular processes such as cell cycling and signal transduction. Changes in some of the components of this pathway have been implicated in various conditions, including cancer and infectious diseases such as malaria. The success of therapies based on proteasome inhibitors has been shown in human clinical trials. In addition to its proven tractability, the essentiality of the Plasmodium falciparum UPS underlines its potential as a source of targets to identify new antimalarial treatments. Two assays, previously developed to quantify the parasite protein ubiquitylation levels in a high throughput format, have been used to identify compounds that inhibit parasite growth by targeting P. falciparum UPS. Among the positive hits, specific inhibitors of the P. falciparum proteasome have been identified and characterized. Hits identified using this approach may be used as starting points for development of new antimalarial drugs. They may also be used as tools to further understand proteasome function and to identify new targets in P. falciparum UPS.

中文翻译：

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识别破坏疟疾中泛素蛋白酶体系统的小分子。

泛素蛋白酶体系统（UPS）是真核细胞中的主要蛋白水解途径之一，在关键细胞过程（例如细胞周期和信号转导）中起着至关重要的作用。该途径中某些成分的变化与多种疾病有关，包括癌症和疟疾等传染性疾病。在人类临床试验中已经证明了基于蛋白酶体抑制剂的治疗方法的成功。除已证明的易处理性外，恶性疟原虫UPS的必要性还强调了其作为确定新的抗疟疾治疗目标的来源的潜力。先前已开发出两种测定方法，用于以高通量形式量化寄生虫蛋白的泛素化水平，已用于鉴定通过靶向抑制寄生虫生长的化合物恶性疟原虫UPS。在阳性结果中，已经鉴定并鉴定了恶性疟原虫蛋白酶体的特异性抑制剂。使用这种方法确定的命中可以用作开发新抗疟药的起点。它们还可以用作进一步了解蛋白酶体功能和识别恶性疟原虫UPS中新靶标的工具。