Identification by functional proteomics of a deubiquitinating/deNeddylating enzyme in Plasmodium falciparum
Identification by functional proteomics of a deubiquitinating/deNeddylating enzyme in Plasmodium falciparum
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DOI：
10.1111/j.1365-2958.2006.05307.x
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发表时间：
2006-09-01
影响因子：
3.6
通讯作者：
Ploegh, Hidde L.
中科院分区：
文献类型：
--
作者：
Artavanis-Tsakonas, Katerina;Misaghi, Shahram;Ploegh, Hidde L.
泛素化是一种翻译后修饰，涉及多种细胞功能，包括转录调控、蛋白质降解和膜蛋白运输。泛素和作用于它的酶，虽然在真核生物中是保守的和必需的，但在寄生虫中还没有得到很好的研究，尽管对几种寄生虫基因组进行了测序。几个假定的泛素水解酶已被确定在恶性疟原虫的基础上的序列同源性，没有证据的表达或功能。在这里，我们确定了第一个去泛素化酶在恶性疟原虫，PfUCH 54，其活性。我们发现，PfUCH 54也有deddylating活性，如哺乳动物Nedd8为基础的探针测定。这种活性在PfUCH 54的哺乳动物同系物中不存在。鉴于寄生虫膜蛋白运输以及蛋白质降解在该寄生虫毒力中的重要性，该酶家族可能代表了对该疾病进行药物干预的靶点。
Ubiquitination is a post-translational modification implicated in a variety of cellular functions, including transcriptional regulation, protein degradation and membrane protein trafficking. Ubiquitin and the enzymes that act on it, although conserved and essential in eukaryotes, have not been well studied in parasites, despite sequencing of several parasite genomes. Several putative ubiquitin hydrolases have been identified in Plasmodium falciparum based on sequence homology alone, with no evidence of expression or function. Here we identify the first deubiquitinating enzyme in P. falciparum, PfUCH54, by its activity. We show that PfUCH54 also has deNeddylating activity, as assayed by a mammalian Nedd8-based probe. This activity is absent from mammalian homologues of PfUCH54. Given the importance of parasitic membrane protein trafficking as well as protein degradation in the virulence of this parasite, this family of enzymes may represent a target for pharmacological intervention with this disease.