title: Cooperation of multiple chaperones required for the assembly of mammalian 20S proteasomes.
abstract: The 20S proteasome is a catalytic core of the 26S proteasome, a central enzyme in the degradation of ubiquitin-conjugated proteins. It is composed of 14 distinct gene products that form four stacked rings of seven subunits each, alpha(1-7)beta(1-7)beta(1-7)alpha(1-7). It is reported that the biogenesis of mammalian 20S proteasomes is assisted by proteasome-specific chaperones, named PAC1, PAC2, and hUmp1, but the details are still unknown. Here, we report the identification of a chaperone, designated PAC3, as a component of alpha rings. Although it can intrinsically bind directly to both alpha and beta subunits, PAC3 dissociates before the formation of half-proteasomes, a process coupled with the recruitment of beta subunits and hUmp1. Knockdown of PAC3 impaired alpha ring formation. Further, PAC1/2/3 triple knockdown resulted in the accumulation of disorganized half-proteasomes that are incompetent for dimerization. Our results describe a cooperative system of multiple chaperones involved in the correct assembly of mammalian 20S proteasomes.
authors.affiliation: Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hirano
authors.forename: Hidemi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Klavs B
authors.initials: KB
authors.lastname: Hendil
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Niwa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Kasahara
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: D002460:Cell Line; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis / Q000378:metabolism*; D034741:RNA, Small Interfering
chemical_list: D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D046988:Proteasome Endopeptidase Complex