The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention.
The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention.
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DOI：
10.2174/138920310791824057
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发表时间：
2010-09
影响因子：
2.8
通讯作者：
Dou QP
中科院分区：
文献类型：
--
作者：
Chen D;Dou QP
蛋白酶体是位于真核细胞胞浆和细胞核中的大型多催化蛋白酶复合物。泛素-蛋白酶体系统负责大多数细胞内蛋白的降解，因此在包括细胞周期进展、增殖、分化、血管生成和凋亡的关键细胞过程中发挥重要的调节作用。蛋白酶体活性的改变除了涉及正常的细胞功能和稳态外，还有助于多种临床疾病的病理状态，包括炎症、神经变性和癌症。已有研究表明，人癌细胞具有较高水平的蛋白酶体活性，并且对蛋白酶体抑制剂的敏感性高于正常细胞，这表明抑制泛素-蛋白酶体系统可作为一种新的癌症治疗方法。本文综述了蛋白酶体复合物的研究进展，包括蛋白酶体的结构和催化活性，各种蛋白酶体抑制剂的性质和作用机制，以及蛋白酶体抑制剂作为新型抗癌药物的临床研究进展。
Proteasomes are large multicatalytic proteinase complexes located in the cytosol and the nucleus of eukaryotic cells. The ubiquitin-proteasome system is responsible for the degradation of most intracellular proteins and therefore plays an essential regulatory role in critical cellular processes including cell cycle progression, proliferation, differentiation, angiogenesis and apoptosis. Besides involving in normal cellular functions and homeostasis, the alteration of proteasomal activity contributes to the pathological states of several clinical disorders including inflammation, neurodegeneration and cancer. It has been reported that human cancer cells possess elevated level of proteasome activity and are more sensitive to proteasome inhibitors than normal cells, indicating that the inhibition of the ubiquitin-proteasome system could be used as a novel approach for cancer therapy. In this review we summarize several specific aspects of research for the proteasome complex, including the structure and catalytic activities of the proteasome, properties and mechanisms of action of various proteasome inhibitors, and finally the clinical development of proteasome inhibitors as novel anticancer agents.