PDF(Pubmed)
Abstract：
Protein homeostasis is the basis of normal life activities, and the proteasome family plays an extremely important function in this process. The proteasome 20S is a concentric circle structure with two α rings and two β rings overlapped. The proteasome 20S can perform both ATP-dependent and non-ATP-dependent ubiquitination proteasome degradation by binding to various subunits (such as 19S, 11S, and 200 PA), which is performed by its active subunit β1, β2, and β5. The proteasome can degrade misfolded, excess proteins to maintain homeostasis. At the same time, it can be utilized by tumors to degrade over-proliferate and unwanted proteins to support their growth. Proteasomes can affect the development of tumors from several aspects including tumor signaling pathways such as NF-κB and p53, cell cycle, immune regulation, and drug resistance. Proteasome-encoding genes have been found to be overexpressed in a variety of tumors, providing a potential novel target for cancer therapy. In addition, proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib have been put into clinical application as the first-line treatment of multiple myeloma. More and more studies have shown that it also has different therapeutic effects in other tumors such as hepatocellular carcinoma, non-small cell lung cancer, glioblastoma, and neuroblastoma. However, proteasome inhibitors are not much effective due to their tolerance and singleness in other tumors. Therefore, further studies on their mechanisms of action and drug interactions are needed to investigate their therapeutic potential.
摘要：
蛋白质稳态是正常生命活动的基础,而蛋白酶体家族在这一过程中起着极其重要的作用。蛋白酶体20S是具有两个α环和两个β环重叠的同心圆结构。蛋白酶体20S可以通过与各种亚基（例如19S，11S,和200PA），其通过其活性亚基β1、β2和β5进行。蛋白酶体可以降解错误折叠的，过量的蛋白质来维持体内平衡。同时,它可以被肿瘤用来降解过度增殖的蛋白质和不需要的蛋白质来支持它们的生长。蛋白酶体可以从NF-κB和p53等肿瘤信号通路、细胞周期、免疫调节，和抗药性。已发现蛋白酶体编码基因在多种肿瘤中过表达,为癌症治疗提供了一个潜在的新靶点。此外,蛋白酶体抑制剂，如硼替佐米，Carfilzomib,和艾沙佐米已作为多发性骨髓瘤的一线治疗方法投入临床应用。越来越多的研究表明，它在肝细胞癌等其他肿瘤中也有不同的治疗效果，非小细胞肺癌,胶质母细胞瘤,和神经母细胞瘤.然而,蛋白酶体抑制剂由于它们在其他肿瘤中的耐受性和单一性，效果不大。因此,需要进一步研究它们的作用机制和药物相互作用,以研究它们的治疗潜力.
