プロテアソームの分子集合機構

抄録

The 26S proteasome is a multisubunit protease responsible for regulated proteolysis in eukaryotic cells. The catalytic activities are carried out by the core 20S proteasome. The 20S proteasome is composed of 28 subunits arranged in a cylindrical particle as four heteroheptameric rings, α _1-7 β _1-7 β _1-7 α _1-7. However, the mechanism responsible for the assembly of such complex structure remains elusive. Recently, we found three novel chaperones involved in the maturation of mammalian 20S proteasomes, designated Proteasome Assembling Chaperone-1 (PAC1), PAC2, and PAC3. These three molecules associate with precursor 20S proteasomes. Specifically, they are required for α-ring and subsequent half-proteasome formation. Their knockdown by siRNA causes abnormally assembled proteasome precursors, resulting in poor 20S proteasome maturation. The previously known proteasome maturation factor hUmp1 (also called POMP or proteassemblin) helps the dimerization of half-proteasomes, and 20S proteasome formation is completed. Based on these findings, we propose a multistep-ordered mechanism for the assembly for mammalian proteasomes.