Proteasome and Its Inhibitors



The Proteasome is the major degradation pathway where the misfolded proteins during protein synthesis and other proteins are proteolyzed. It is present in all eukaryotic cells, archaea, and some bacteria. It is a multicatalytic protease, composed of multiple catalytic and regulatory proteins. It possesses three or four different peptidase activities, including trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing activities. Most of proteins are ubiquitinated prior to the proteasome degradation. It is estimated that about 20% of 26S proteasomes are engaged in protein degradation in the absence of proteotoxic stress [1].
Proteasome inhibitors have found applications as therapeutic drugs against diseases like cancer, and wide application in laboratory research. Bortezomib, also called PS-341, Velcade, and MG-341, is an FDA-approved drug for multiple myeloma and mantle cell lymphoma. It is also used in laboratory experiments to inhibit proteasome activity [2]. Several other proteasome inhibitors are proposed to be useful drugs or are undergoing clinical trials and testing, including disulfiram, epigallocatechin-3-gallate, Salinosporamide A, carfilzomib, ONX 0912, CEP-18770, and MLN9708. Silva MC et al. pre-treated neuronal cells with carfilzomib to inhibit proteasome to understand the effect of tau degrader QC-01–175 [3]. GNF6702 inhibits the kinetoplastid proteasome (while possessing no activity against mammalian proteasome) and has been proposed to represent a new class of drugs for Chagas disease, leishmaniasis, and sleeping sickness [4].
Labome surveys literature for antibodies, instruments, and other reagents. Among the formal publications that contain the explicit references to proteasome inhibitors, MG132 is the predominant choice cited among the articles. Table 1 lists the number of publications for major proteasome inhibitors. Major features of these three proteasome inhibitors are listed in Table 2.