JAMP optimizes ERAD to protect cells from unfolded proteins.
JAMP optimizes ERAD to protect cells from unfolded proteins.
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DOI：
10.1091/mbc.e08-08-0839
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发表时间：
2008-11
影响因子：
3.3
通讯作者：
M. Tcherpakov;L. Broday;A. Delaunay;Takayuki Kadoya;A. Khurana;H. Erdjument-Bromage;P. Tempst;Xiao-Bo Qiu;G. Demartino;Z. Ronai
中科院分区：
文献类型：
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作者：
M. Tcherpakov;L. Broday;A. Delaunay;Takayuki Kadoya;A. Khurana;H. Erdjument-Bromage;P. Tempst;Xiao-Bo Qiu;G. Demartino;Z. Ronai
清除内质网中错误折叠的蛋白质是维持细胞内环境平衡的关键。这个过程需要协调识别，内质网-胞浆易位，最后泛素化依赖的蛋白酶体降解。在这里，我们识别了一种内质网驻留的七跨膜蛋白(JAMP)，它连接内质网伴侣、通道蛋白、泛素连接酶和26S蛋白酶体亚基，从而优化错误折叠蛋白的降解。JAMP表达增加促进蛋白酶体在内质网的定位，伴随着对特定ER驻留的错误折叠蛋白的降解，而抑制JAMP则促进相反的反应。相应地，缺失JAMP-1的秀丽线虫菌株对ER胁迫和UPR增加表现出超敏反应。利用生化和遗传学方法，我们确定JAMP是协调清除错误折叠蛋白质从内质网中的重要成分。
Clearance of misfolded proteins from the ER is central for maintenance of cellular homeostasis. This process requires coordinated recognition, ER-cytosol translocation, and finally ubiquitination-dependent proteasomal degradation. Here, we identify an ER resident seven-transmembrane protein (JAMP) that links ER chaperones, channel proteins, ubiquitin ligases, and 26S proteasome subunits, thereby optimizing degradation of misfolded proteins. Elevated JAMP expression promotes localization of proteasomes at the ER, with a concomitant effect on degradation of specific ER-resident misfolded proteins, whereas inhibiting JAMP promotes the opposite response. Correspondingly, a jamp-1 deleted Caenorhabditis elegans strain exhibits hypersensitivity to ER stress and increased UPR. Using biochemical and genetic approaches, we identify JAMP as important component for coordinated clearance of misfolded proteins from the ER.