Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Chemistry, Surface Chemistry Research Laboratory, Iran University of Science and Technology, PO Box 16846-13114, Tehran, Iran.
Open Biol. 2021 Apr;11(4):200390. doi: 10.1098/rsob.200390. Epub 2021 Apr 28.
Despite all the other cells that have the potential to prevent cancer development and metastasis through tumour suppressor proteins, cancer cells can upregulate the ubiquitin-proteasome system (UPS) by which they can degrade tumour suppressor proteins and avoid apoptosis. This system plays an extensive role in cell regulation organized in two steps. Each step has an important role in controlling cancer. This demonstrates the importance of understanding UPS inhibitors and improving these inhibitors to foster a new hope in cancer therapy. UPS inhibitors, as less invasive chemotherapy drugs, are increasingly used to alleviate symptoms of various cancers in malignant states. Despite their success in reducing the development of cancer with the lowest side effects, thus far, an appropriate inhibitor that can effectively inactivate this system with the least drug resistance has not yet been fully investigated. A fundamental understanding of the system is necessary to fully elucidate its role in causing/controlling cancer. In this review, we first comprehensively investigate this system, and then each step containing ubiquitination and protein degradation as well as their inhibitors are discussed. Ultimately, its advantages and disadvantages and some perspectives for improving the efficiency of these inhibitors are discussed.
尽管其他细胞有可能通过肿瘤抑制蛋白来预防癌症的发生和转移,但癌细胞可以通过泛素-蛋白酶体系统 (UPS) 上调肿瘤抑制蛋白,从而降解肿瘤抑制蛋白并避免细胞凋亡。该系统在两个步骤的细胞调节中发挥着广泛的作用。每个步骤在控制癌症方面都起着重要的作用。这表明理解 UPS 抑制剂并改进这些抑制剂以在癌症治疗中带来新的希望的重要性。UPS 抑制剂作为侵袭性较小的化疗药物,越来越多地用于缓解恶性肿瘤状态下各种癌症的症状。尽管它们在降低癌症发展和副作用方面取得了成功,但迄今为止,尚未对能够有效灭活该系统且耐药性最低的适当抑制剂进行充分研究。因此,全面了解该系统对于充分阐明其在引发/控制癌症中的作用是必要的。在这篇综述中,我们首先全面研究了该系统,然后讨论了包含泛素化和蛋白降解以及它们的抑制剂的各个步骤。最终,讨论了其优缺点以及提高这些抑制剂效率的一些观点。