Cooperation of multiple chaperones required for the assembly of mammalian 20S proteasomes

被引:118
作者
Hirano, Yuko
Hayashi, Hidemi
Lemura, Shun-ichiro
Hendil, Klavs B.
Niwa, Shin-ichiro
Kishimoto, Toshilhiko
Kasahara, Masanori
Natsume, Tohru
Tanaka, Keiji
Murata, Shigeo [1 ]
机构
[1] Tokyo Metropolitan Inst Med Sci, Lab Frontier Sci, Core Technol & Res Ctr, Bunkyo Ku, Tokyo 1138613, Japan
[2] Toho Univ, Fac Sci, Proteome Anal Ctr, Funabashi, Chiba 2748510, Japan
[3] Toho Univ, Fac Sci, Dept Biomol Sci, Funabashi, Chiba 2748510, Japan
[4] Link Genom Inc, Chuo Ku, Tokyo 1030024, Japan
[5] Natl Inst Adv Ind Sci & Technol, Biol Informat Res Ctr, Kohtoh Ku, Tokyo 1350064, Japan
[6] Univ Copenhagen, Inst Mol Biol & Biophys, DK-2100 Copenhagen, Denmark
[7] Hokkaido Univ, Grad Sch Med, Dept Pathol, Sapporo, Hokkaido 0608638, Japan
[8] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan
基金
日本科学技术振兴机构; 日本学术振兴会;
关键词
D O I
10.1016/j.molcel.2006.11.015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:977 / 984
页数:8
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