The 26S proteasome is the major proteolytic machine for breaking down cytosolic and nuclear proteins in eukaryotes. Due to the lack of a suitable assay, it is difficult to measure routinely and quantitatively the breakdown of proteins by the 26S proteasome in vitro. In the present study, we developed an assay to monitor proteasome-mediated protein degradation. Using this assay, we discovered that epidithiodiketopiperazine (ETPs) blocked the degradation of our model substrate in vitro. Further characterization revealed that ETPs inhibited proteasome function by targeting the essential proteasomal deubiquitinase Rpn11 (POH1/PSMD14). ETPs also inhibited other JAMM (JAB1/MPN/Mov34 metalloenzyme) proteases such as Csn5 and AMSH. An improved ETP with fewer non-specific effects, SOP11, stabilized a subset of proteasome substrates in cells, induced the unfolded protein response, and led to cell death. SOP11 represents a class of Rpn11 inhibitor and provides an alternative route to develop proteasome inhibitors.
Pubmed ID: 30146242 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets c-Myc antibody [Y69]
View all literature mentionsThis monoclonal targets IKB alpha
View all literature mentionsThis monoclonal targets Histone H2A.X pSer139
View all literature mentionsThis monoclonal targets XBP-1s
View all literature mentionsThis recombinant monoclonal targets MDM2
View all literature mentionsThis monoclonal targets Cleaved PARP (Asp214)
View all literature mentionsThis monoclonal targets BiP (C50B12) Rabbit mAb
View all literature mentionsThis monoclonal targets PERK (D11A8) Rabbit mAb
View all literature mentionsThis monoclonal targets CHOP
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets GAPDH
View all literature mentionsThis monoclonal targets raised against amino acids 37-336 of Nrf2 of human origin
View all literature mentionsThis monoclonal targets TCF11/NRF1 (D5B10) Rabbit mAb
View all literature mentionsThis polyclonal targets Ubiquitin pAb
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets c-Myc antibody [Y69]
View all literature mentions