Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
J Cell Biol. 2012 Nov 12;199(4):583-8. doi: 10.1083/jcb.201210077.
The proteasome is the primary site for protein degradation in mammalian cells, and proteasome inhibitors have been invaluable tools in clarifying its cellular functions. The anticancer agent bortezomib inhibits the major peptidase sites in the proteasome's 20S core particle. It is a "blockbuster drug" that has led to dramatic improvements in the treatment of multiple myeloma, a cancer of plasma cells. The development of proteasome inhibitors illustrates the unpredictability, frustrations, and potential rewards of drug development but also emphasizes the dependence of medical advances on basic biological research.
蛋白酶体是哺乳动物细胞中蛋白质降解的主要场所，蛋白酶体抑制剂在阐明其细胞功能方面是非常有价值的工具。抗癌药物硼替佐米抑制蛋白酶体 20S 核心颗粒中主要的肽酶位点。它是一种“重磅炸弹药物”，导致多发性骨髓瘤（一种浆细胞瘤癌症）治疗的显著改善。蛋白酶体抑制剂的开发说明了药物开发的不可预测性、挫折和潜在回报，但也强调了医学进步对基础生物学研究的依赖。
