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哈佛大学医学院细胞生物学系，普林斯顿大学分子生物学系Lewis Thomas实验室的研究者在最新的Nature在线版上发表文章，Chaperone-mediated pathway of proteasome regulatory particle assembly。 蛋白酶体（proteasome）是一种在真核细胞内控制多种生命进程的蛋白酶。在蛋白酶体降解泛素蛋白的开始阶段，其调节性颗粒（regulatory particle，RP）首先解开酶作用底物的折叠，然后将酶作用底物转移到蛋白酶体的核心颗粒位置（core particle，CP）。调节性颗粒（regulatory particle，RP）具有19个亚单位，目前RP亚单位的装配过程一直不明。 在本研究中，研究人员以酵母Saccharomyces cerevisiae为模型，研究蛋白酶体，结果发现，有三个蛋白与蛋白酶体的RP有关联，这三个蛋白分别是Nas6，Rpn14和Hsm3。如果表达这些蛋白的基因发生突变，会导致蛋白酶体失去功能。蛋白酶体的RP装配过程受多种伴侣分子的调控。 推荐原始出处： Nature advance online publication 1 May 2009 | doi:10.1038/nature08063 Chaperone-mediated pathway of proteasome regulatory particle assembly Jeroen Roelofs1, Soyeon Park1, Wilhelm Haas1, Geng Tian1, Fiona E. McAllister1, Ying Huo1, Byung-Hoon Lee1, Fan Zhang2, Yigong Shi2, Steven P. Gygi1 & Daniel Finley1 1 Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA 2 Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA The proteasome is a protease that controls diverse processes in eukaryotic cells. Its regulatory particle (RP) initiates the degradation of ubiquitin–protein conjugates by unfolding the substrate and translocating it into the proteasome core particle (CP) to be degraded1. The RP has 19 subunits, and their pathway of assembly is not understood. Here we show that in the yeast Saccharomyces cerevisiae three proteins are found associated with RP but not with the RP–CP holoenzyme: Nas6, Rpn14 and Hsm3. Mutations in these genes confer proteasome loss-of-function phenotypes, despite their virtual absence from the holoenzyme. These effects result from deficient RP assembly. Thus, Nas6, Rpn14 and Hsm3 are RP chaperones. The RP contains six ATPases–the Rpt proteins–and each RP chaperone binds to the carboxy-terminal domain of a specific Rpt. We show in an accompanying study2 that RP assembly is templated through the Rpt C termini, apparently by their insertion into binding pockets in the CP. Thus, RP chaperones may regulate proteasome assembly by directly restricting the accessibility of Rpt C termini to the CP. In addition, competition between the CP and RP chaperones for Rpt engagement may explain the release of RP chaperones as proteasomes mature. (责任编辑：Doctor001) |
