Novel strategies to target the ubiquitin proteasome system in multiple myeloma.
Novel strategies to target the ubiquitin proteasome system in multiple myeloma.
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DOI：
10.18632/oncotarget.6658
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发表时间：
2016-02-09
期刊：
影响因子：
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通讯作者：
Van Valckenborgh E
中科院分区：
文献类型：
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作者：
Lub S;Maes K;Menu E;De Bruyne E;Vanderkerken K;Van Valckenborgh E
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，其特征是骨髓（BM）中浆细胞的积累。蛋白酶体抑制剂硼替佐米治疗MM的成功突出了泛素蛋白酶体系统（UPS）在这种特殊癌症中的重要性。尽管MM患者的生存期延长，但仍有大量患者复发或对治疗产生耐药性。这强调了开发和研究新的靶点来改善MM治疗的重要性。UPS通过靶向破坏蛋白质在不同的细胞过程中发挥重要作用。泛素化过程由酶组成，这些酶将泛素转移到针对它们的蛋白酶体降解的蛋白质上。一种新兴且有希望的方法是针对UPS的更多疾病特异性成分，以减少副作用并克服耐药性。在本文中，我们将重点介绍UPS的不同组成部分，如泛素活化酶E1、泛素结合酶E2、E3泛素连接酶、去泛素化酶（DUBs）和蛋白酶体。我们将讨论它们在MM中的作用以及在MM治疗药物发现中的意义。
Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of plasma cells in the bone marrow (BM). The success of the proteasome inhibitor bortezomib in the treatment of MM highlights the importance of the ubiquitin proteasome system (UPS) in this particular cancer. Despite the prolonged survival of MM patients, a significant amount of patients relapse or become resistant to therapy. This underlines the importance of the development and investigation of novel targets to improve MM therapy. The UPS plays an important role in different cellular processes by targeted destruction of proteins. The ubiquitination process consists of enzymes that transfer ubiquitin to proteins targeting them for proteasomal degradation. An emerging and promising approach is to target more disease specific components of the UPS to reduce side effects and overcome resistance. In this review, we will focus on different components of the UPS such as the ubiquitin activating enzyme E1, the ubiquitin conjugating enzyme E2, the E3 ubiquitin ligases, the deubiquitinating enzymes (DUBs) and the proteasome. We will discuss their role in MM and the implications in drug discovery for the treatment of MM.