多种与蛋白酶体相互作用的蛋白质协助酵母19S调节颗粒的组装。

Multiple proteasome-interacting proteins assist the assembly of the yeast 19S regulatory particle.

作者信息

Saeki Yasushi, Toh-E Akio, Kudo Tai, Kawamura Hitomi, Tanaka Keiji

机构信息

Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.

出版信息

Cell. 2009 May 29;137(5):900-13. doi: 10.1016/j.cell.2009.05.005. Epub 2009 May 14.

DOI:10.1016/j.cell.2009.05.005

PMID:19446323

Abstract

The 26S proteasome is 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.

摘要

26S蛋白酶体是一种高度保守的多亚基蛋白酶，可降解真核细胞中泛素化的蛋白质。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。尽管CP组装的机制已得到充分描述，但RP组装的机制在很大程度上尚不清楚。在这里，我们表明四种蛋白酶体相互作用蛋白（PIP），即Nas2/p27、Nas6/ankyrin、Rpn14/PAAF1和Hsm3/S5b，与RP的特定Rpt亚基结合并在遗传上相互作用。缺乏这些PIP会导致26S蛋白酶体在早期组装缺陷，这表明这些蛋白质是真正的RP伴侣蛋白。每个RP伴侣蛋白形成了不同的特定基础组件亚组装体，并将它们护送成熟的RP。我们的结果表明，RP组装是一个由多个蛋白酶体专用伴侣蛋白精心编排的高度有组织且复杂的过程。