Salinosporamides A and B Inhibit Proteasome Activity and Delay the Degradation of N-end Rule Model Substrates

Bulletin of the Korean chemical society

Won Hoon Choi¹  Min Jae Lee¹  Dae in Bang¹  Seong-Hwan Kim¹  Dong-Chan Oh¹  Seung Kyun Shin¹ 

关键词: Degradation;    Ubiquitin;    Proteasome;    Inhibitor;    N-end rule;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

The proteasome, which is highly evolutionarily conserved, is responsible for the degradation of most shortlived proteins in cells. Small-molecule inhibitors targeting the proteasome`s degradative activity have been extensively developed as lead compounds for various human diseases. An exemplified molecule is bortezomib, which was approved by FDA in 2003 for the treatment of multiple myeloma. Here, using transiently and stably expressed N-end rule model substrates in mammalian cells, we evaluated and identified that salinosporamide A and salinosporamide B effectively inhibited the proteasomal degradation. Considering that a variety of proteasome substrates are implicated in the pathogenesis of many diseases, they have the potential to be clinically applicable as therapeutic agents.

【 授权许可】

Unknown