哈佛大學(xué)醫(yī)學(xué)院細(xì)胞生物學(xué)系,，普林斯頓大學(xué)分子生物學(xué)系Lewis Thomas實(shí)驗(yàn)室的研究者在最新的Nature在線版上發(fā)表文章,，Chaperone-mediated pathway of proteasome regulatory particle assembly。
蛋白酶體（proteasome）是一種在真核細(xì)胞內(nèi)控制多種生命進(jìn)程的蛋白酶,。在蛋白酶體降解泛素蛋白的開(kāi)始階段,，其調(diào)節(jié)性顆粒（regulatory particle,，RP）首先解開(kāi)酶作用底物的折疊,，然后將酶作用底物轉(zhuǎn)移到蛋白酶體的核心顆粒位置（core particle，CP）,。調(diào)節(jié)性顆粒（regulatory particle,，RP）具有19個(gè)亞單位，目前RP亞單位的裝配過(guò)程一直不明,。
在本研究中,，研究人員以酵母Saccharomyces cerevisiae為模型，研究蛋白酶體,，結(jié)果發(fā)現(xiàn),，有三個(gè)蛋白與蛋白酶體的RP有關(guān)聯(lián)，這三個(gè)蛋白分別是Nas6,，Rpn14和Hsm3,。如果表達(dá)這些蛋白的基因發(fā)生突變，會(huì)導(dǎo)致蛋白酶體失去功能,。蛋白酶體的RP裝配過(guò)程受多種伴侶分子的調(diào)控,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
