Cooperation of multiple chaperones required for the assembly of mammalian 20S proteasomes
Cooperation of multiple chaperones required for the assembly of mammalian 20S proteasomes
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DOI：
10.1016/j.molcel.2006.11.015
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发表时间：
2006-12-28
期刊：
影响因子：
16
通讯作者：
Murata, Shigeo
中科院分区：
文献类型：
--
作者：
Hirano, Yuko;Hayashi, Hidemi;Murata, Shigeo
20S蛋白酶体是26S蛋白酶体的催化核心，26S蛋白酶体是降解泛素结合蛋白的中心酶。它由14个不同的基因产物组成，形成四个堆叠的环，每个环有七个亚基，分别是α(1-7)β(1-7)β(1-7)α(1-7)。据报道，哺乳动物20S蛋白酶体的生物发生受到蛋白酶体特异的伴侣蛋白PAC1、PAC2和hUmp1的辅助，但具体细节仍不清楚。在这里，我们报告了一个被命名为PAC3的伴侣分子的鉴定，它是阿尔法环的一个组成部分。尽管PAC3本质上可以直接与α和β亚基结合，但它在半蛋白酶体形成之前就解离了，这个过程与β亚基和hUmp1的招募有关。PAC3基因敲除会影响阿尔法环的形成。此外，PAC1/2/3三重敲除导致不具备二聚化能力的杂乱无章的半蛋白酶体的积累。我们的结果描述了一个由多个伴侣组成的合作系统，该系统参与哺乳动物20S蛋白酶体的正确组装。
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.