Molecular mechanisms of proteasome assembly

The 26S proteasome is a eukaryotic large protein complex that is essential for regulated protein degradation in collaboration with the ubiquitin system. It consists of the catalytic 20S proteasome and the 19S regulatory particle, but how this large complex is assembled has been a mystery.Recent studies have unveiled several proteasome-dedicated chaperones that are involved in efficient and correct assembly of the eukaryotic proteasome.The mammalian proteasome assembling chaperone 1 (PAC1)–PAC2 heterodimer is suggested to be involved in the formation of α-rings, the earliest assembly intermediates to be observed during 20S proteasome biogenesis. At the same time, it prevents aberrant dimerization of α-rings.The yeast proteasome biogenesis-associated 3 (Pba3)–Pba4 heterodimer (and presumably the mammalian PAC3–PAC4 complex) is also involved in α-ring formation by catalysing correct subunit orientation of the α-ring.Yeast ubquitin-mediated proteolysis 1 (Ump1) and its human orthologue UMP1 have an important role in the dimerization of half-proteasomes. UMP1 is also shown to be required for β-ring formation on the α-ring in cooperation with the propeptides and carboxy-terminal extensions of β-subunits.Compared with the 20S proteasome, the assembly of the 19S RP is largely unknown, but several molecules that affect the integrity of the 19S RP have been reported.