Multiple Proteasome-Interacting Proteins Assist the Assembly of the Yeast 19S Regulatory Particle
Multiple Proteasome-Interacting Proteins Assist the Assembly of the Yeast 19S Regulatory Particle
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DOI：
10.1016/j.cell.2009.05.005
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发表时间：
2009-05-29
期刊：
影响因子：
64.5
通讯作者：
Tanaka, Keiji
中科院分区：
文献类型：
--
作者：
Saeki, Yasushi;Toh-e, Akio;Tanaka, Keiji
26S蛋白酶体是一种高度保守的多亚基蛋白酶，在真核细胞中降解泛素化蛋白。26S蛋白酶体由蛋白水解核心颗粒（CP）和一个或两个19S调节颗粒（rp）组成。虽然CP组装的机制已被很好地描述，但RP组装的机制在很大程度上是未知的。在这里，我们发现四个蛋白酶体相互作用蛋白（PIPs）， Nas2/p27, Nas6/gankyrin， Rpn14/PAAF1和Hsm3/S5b，结合RP的特异性Rpt亚基并相互作用。缺乏这些pip会导致26S蛋白酶体在早期阶段的组装缺陷，这表明这些蛋白质是真正的RP伴侣。每个RP伴侣形成不同的特定的碱基组件亚组件，并护送它们到成熟的RP。我们的结果表明，RP组装是由多个蛋白酶体专用伴侣精心策划的高度有组织和复杂的过程。
The 26S proteasomeis 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.