Proteasome inhibitors

Abstract

The proteasome is a large multifunctional proteolytic complex responsible for non-lysosomal protein degradation [1-3]. The form of the enzyme most frequent-ly studied is the 20S proteasome, a 700 kDa complex which catalyzes at least five proteolytic activities. The 20S proteasome is the catalytic core of the 26S proteasome, a larger particle (2000 kDa) which also contains two copies of a 19S regulatory complex. The 26S form of the proteasome catalyzes ATP-dependent hydrolysis of ubiquitinated proteins, while the 20S proteasome is not ATP-dependent. The enzyme is conserved from archaebacteria and eubacteria, which contain only the 20S proteasome, through eukaryotes, which express both 20S and 26S forms of the enzyme [4]. The proteasome is located in both the cytosol and nucleus of eukaryotic cells and is a predominant cellular component, comprising up to 1% of the total protein in most cells. The enzyme plays a major role in the degrada-tion of misfolded, damaged or abnormal proteins, as well as in the modulation of levels of key cell signaling regulators [5]. The activity of the proteasome is highly regulated, and any deregulation has the potential to lead to pathological condi-tions.KeywordsProteasome InhibitorBoronic AcidBoronic EsterVinyl SulfonePeptide AldehydeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.