Multiple proteasome-interacting proteins assist the assembly of the yeast 19S regulatory particle.
The 26S proteasome is a highly conserved multisubunit protease that degrades ubiquitinated proteins in eukaryotic cells. The 26S proteasome consists of the proteolytic core particle (CP) and one or two 19S regulatory particles (RPs). Although the mechanisms of CP assembly are well described, the mechanism of RP assembly is largely unknown. Here, we show that four proteasome-interacting proteins (PIPs), Nas2/p27, Nas6/gankyrin, Rpn14/PAAF1, and Hsm3/S5b, bind specific Rpt subunits of the RP and interact each other genetically. Lack of these PIPs resulted in defective assembly of the 26S proteasome at an early stage, suggesting that these proteins are bona fide RP chaperones. Each of the RP chaperones formed distinct specific subassemblies of the base components and escorted them to mature RPs. Our results indicate that the RP assembly is a highly organized and elaborate process orchestrated by multiple proteasome-dedicated chaperones.
Saeki
Yasushi
Y
Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
Toh-E
Akio
A
Kudo
Tai
T
Kawamura
Hitomi
H
Tanaka
Keiji
K
D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D018832:Molecular Chaperones; C114551:NAS6 protein, S cerevisiae; C403591:PSMD10 protein, human; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13