蛋白酶体及其抑制剂的研究进展

Study progress of proteasome and its inhibitor

蛋白酶体抑制剂通过阻断泛素蛋白酶体通路,影响细胞内多个周期蛋白的降解,诱导细胞凋亡。体内外试验已显示蛋白酶体抑制剂具有广泛抗肿瘤作用。蛋白酶体抑制剂Bortezomib已通过美国FDA批准应用于临床治疗多发性骨髓瘤。该文就蛋白酶体结构、蛋白酶体抑制剂作用途径、促凋亡作用机制的研究成果和现阶段临床应用作一综述。

Protein degradation is fundamental to cell viability, selective elimination of regulatory proteins in the cell is an effectire mechanism for regulating vital cell processes. Rapid proteasomal protein degradation is key to activation of repression of many cellular processes, including cell-cycle progression and apoptosis. Bortezomib as a proteasome inhibitor has been ap- proved by FDA for multiple myeloma treatment. This review summarizes current knowledge of the structure and function of the proteasome and its targets. In addition, preclinical findings obtained with Bortezomib are reviewed, and existing clinical data on Bortezomib are presented.