Chung Duk-Won Doug, Le Roch Karine G
University of California Riverside, Department of Cell Biology & Neuroscience, 900 University Avenue, Genomics Building Room 2121B, Riverside, CA 92521, USA.
Infect Disord Drug Targets. 2010 Jun;10(3):158-64. doi: 10.2174/187152610791163345.
The human malarial parasite, Plasmodium falciparum, is responsible for one of the most infectious diseases of the world and is quickly gaining resistance to the commonly used antimalarial treatments. New data are continually reinforcing the idea that biological functions associated with the ubiquitin proteasome system (UPS) are not just limited to non-lysomal degradation of proteins but consist of a wide array of regulatory mechanisms such as cell cycle progression, transcriptional regulation, gene expression and trafficking. While there is much effort in understanding the UPS in many eukaryotic organisms, the Plasmodium UPS has been relatively understudied despite its potential as a therapeutic drug target. However, in vitro proteasome inhibitors studies have confirmed the essentiality of the UPS in Plasmodia with limited toxicity to human cell lines. In addition, computational studies have shown that there are a number of ubiquitinating proteins upstream of the proteasome that may serve as parasite-specific drug targets due to their variety and divergences from other eukaryotic species. In this review, we highlight the major findings about Plasmodium's UPS and discuss its possible implications as an effective and specific antimalarial target.
人类疟原虫恶性疟原虫是世界上最具传染性的疾病之一的病原体，并且正在迅速对常用的抗疟疾治疗产生耐药性。新数据不断强化这样一种观点，即与泛素蛋白酶体系统（UPS）相关的生物学功能不仅限于蛋白质的非溶酶体降解，还包括一系列广泛的调节机制，如细胞周期进程、转录调控、基因表达和运输。虽然在许多真核生物中对UPS的理解投入了大量精力，但疟原虫的UPS尽管有作为治疗药物靶点的潜力，却相对研究较少。然而，体外蛋白酶体抑制剂研究已证实UPS在疟原虫中的必要性，且对人类细胞系毒性有限。此外，计算研究表明，蛋白酶体上游有许多泛素化蛋白，由于它们的多样性以及与其他真核物种的差异，可能作为寄生虫特异性药物靶点。在本综述中，我们重点介绍了关于疟原虫UPS的主要发现，并讨论了其作为有效且特异性抗疟疾靶点的可能意义。
