Chen Xin, Yang Qianqian, Xiao Lu, Tang Daolin, Dou Q Ping, Liu Jinbao
Protein Modification and Degradation Lab, School of Basic Medical Sciences, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Cancer Metastasis Rev. 2017 Dec;36(4):655-668. doi: 10.1007/s10555-017-9701-1.
Deubiquitinases (DUBs) play an important role in protein quality control in eukaryotic cells due to their ability to specifically remove ubiquitin from substrate proteins. Therefore, recent findings have focused on the relevance of DUBs to cancer development, and pharmacological intervention on these enzymes has become a promising strategy for cancer therapy. In particular, several DUBs are physically and/or functionally associated with the proteasome and are attractive targets for the development of novel anticancer drugs. The successful clinical application of cisplatin in cancer treatment has prompted researchers to develop various metal-based anticancer agents with new properties. Recently, we have reported that several metal-based drugs, such as the antirheumatic gold agent auranofin (AF), the antifouling paint biocides copper pyrithione (CuPT) and zinc pyrithione (ZnPT), and also our two synthesized complexes platinum pyrithione (PtPT) and nickel pyrithione (NiPT), can target the proteasomal DUBs UCHL5 and USP14. In this review, we summarize the recently reported small molecule inhibitors of proteasomal DUBs, with a focus on discussion of the unique nature of metal-based proteasomal DUB inhibitors and their anticancer activity.
去泛素化酶（DUBs）在真核细胞的蛋白质质量控制中发挥着重要作用，因为它们能够特异性地从底物蛋白上移除泛素。因此，最近的研究发现聚焦于DUBs与癌症发展的相关性，对这些酶进行药物干预已成为一种有前景的癌症治疗策略。特别是，几种DUBs在物理和/或功能上与蛋白酶体相关联，是新型抗癌药物开发的有吸引力的靶点。顺铂在癌症治疗中的成功临床应用促使研究人员开发具有新特性的各种金属基抗癌剂。最近，我们报道了几种金属基药物，如抗风湿金剂金诺芬（AF）、防污漆杀菌剂吡啶硫酮铜（CuPT）和吡啶硫酮锌（ZnPT），以及我们合成的两种配合物吡啶硫酮铂（PtPT）和吡啶硫酮镍（NiPT），可以靶向蛋白酶体DUBs UCHL5和USP14。在这篇综述中，我们总结了最近报道的蛋白酶体DUBs的小分子抑制剂，重点讨论了金属基蛋白酶体DUB抑制剂的独特性质及其抗癌活性。
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