The 26S proteasome is a highly conserved protein degradation machine that consists of the 20S proteasome and 19S regulatory particles, which include 14 and 19 different polypeptides, respectively. How the proteasome components are assembled is a fundamental question towards understanding the process of protein degradation and its functions in diverse biological processes. Several proteasome-dedicated chaperones are involved in the efficient and correct assembly of the 20S proteasome. These chaperones help the initiation and progression of the assembly process by transiently associating with proteasome precursors. By contrast, little is known about the assembly of the 19S regulatory particles, but several hints have emerged.
"Proteasome biogenesis is a highly coordinated multistep event involving the synthesis of all subunits, proteasome assembly , and maturation. Proteasome assembly is not autonomous , but requires chaperones (Murata et al., 2009). In yeast, Ump1 was identified as an assembly factor for the 20S proteasome (Ramos et al., 1998). "
"Indeed, proteasome inhibitors, bortezomib and carfilzomib, have proven effective against cancer cells in animal models and human trials by target the core proteolytic subunits PSMB5, PSMB6, and PSMB7 . Now it is well established that the b4 subunit of the 20 S proteasome, PSMB4, regulates the assembly of the proteasome  . And targeting PSMB4 could potentially prevent the catalytic activity of all three proteolytic subunits . "
[Show abstract][Hide abstract] ABSTRACT: Proteasomal subunit PSMB4, was recently identified as potential cancer driver genes in several tumors. However, the regulatory mechanism of PSMB4 on carcinogenesis process remains unclear. In this study, we investigated the expression and roles of PSMB4 in multiple myeloma (MM). We found a significant up-regulation of PSMB4 in MM plasma and cell lines. Ectopic overexpression of PSMB4 promoted cell growth and colony forming ability of MM cells, whereas inhibition of PSMB4 led to a decrease of such events. Furthermore, our results demonstrated the up-regulation of miR-21 and a positive correlation between the levels of miR-21 and PSMB4 in MM. Re-expression of miR-21 markedly rescued PSMB4 knockdown-mediated suppression of cell proliferation and clone-formation. Additionally, while enforced expression of PSMB4 profoundly increased NF-κB activity and the level of miR-21, PSMB4 knockdown or NF-κB inhibition suppressed miR-21 expression in MM cells. Taken together, our results demonstrated that PSMB4 regulated MM cell growth in part by activating NF-κB-miR-21 signaling, which may represent promising targets for novel specific therapies.
Biochemical and Biophysical Research Communications 02/2015; 458(2). DOI:10.1016/j.bbrc.2015.01.110 · 2.30 Impact Factor
"ATP-dependent ubiquitin-proteasomal proteolysis is responsible for rapid and irreversible protein turnover in the cell (Finley, 2009; Pickart and Cohen, 2004). In mammals, the evolutionarily conserved proteasome contains at least 33 different protein subunits (Bedford et al., 2010; Murata et al., 2009). The 20S core particle (CP) of the proteasome is arranged into fourstacked hetero-oligomeric rings (abba) composed of seven a subunits (a1–a7) and seven b subunits (b1–b7), three of which (b1, b2, and b5) are proteolytically active subunits (Groll et al., 1997). "
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