title: A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes.
abstract: The 26S proteasome is a multisubunit protease responsible for regulated proteolysis in eukaryotic cells. It comprises one catalytic 20S proteasome and two axially positioned 19S regulatory complexes. The 20S proteasome is composed of 28 subunits arranged in a cylindrical particle as four heteroheptameric rings, alpha1-7beta1-7beta1-7alpha1-7 (refs 4, 5), but the mechanism responsible for the assembly of such a complex structure remains elusive. Here we report two chaperones, designated proteasome assembling chaperone-1 (PAC1) and PAC2, that are involved in the maturation of mammalian 20S proteasomes. PAC1 and PAC2 associate as heterodimers with proteasome precursors and are degraded after formation of the 20S proteasome is completed. Overexpression of PAC1 or PAC2 accelerates the formation of precursor proteasomes, whereas knockdown by short interfering RNA impairs it, resulting in poor maturation of 20S proteasomes. Furthermore, the PAC complex provides a scaffold for alpha-ring formation and keeps the alpha-rings competent for the subsequent formation of half-proteasomes. Thus, our results identify a mechanism for the correct assembly of 20S proteasomes.
authors.affiliation: Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hirano
authors.forename: Klavs B
authors.initials: KB
authors.lastname: Hendil
authors.forename: Hideki
authors.initials: H
authors.lastname: Yashiroda
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Nagane
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Hioki
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murata
mesh_terms: D000818:Animals; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011817:Rabbits
chemical_list: D018832:Molecular Chaperones; D021122:Protein Subunits; D034741:RNA, Small Interfering; D046988:Proteasome Endopeptidase Complex