Drosophila Morgue is an F box/ubiquitin conjugase domain protein important for grim-reaper mediated apoptosis.
Drosophila Morgue is an F box/ubiquitin conjugase domain protein important for grim-reaper mediated apoptosis.
复制标题
果蝇 Morgue 是一种 F 盒/泛素缀合酶结构域蛋白，对于死神介导的细胞凋亡非常重要。
DOI：
10.1038/ncb800
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发表时间：
2002
影响因子：
21.3
通讯作者：
Nambu,JohnR
中科院分区：
文献类型：
--
作者：
Wing,JohnP;Schreader,BarbaraA;Yokokura,Takakazu;Wang,Yiqin;Andrews,PaulS;Huseinovic,Neda;Dong,CarolynK;Ogdahl,JustyneL;Schwartz,LawrenceM;White,Kristin;Nambu,JohnR
在果蝇中，细胞凋亡是由Grim-Reaper（Grim-Rpr）和DrosophilaInhibitor of Apoptosis（DIAP）蛋白的综合作用所控制的。抗凋亡DIAP结合半胱天冬酶并抑制其蛋白水解活性。DIAP还与Grim-Rpr蛋白结合，这是一种促进半胱天冬酶活性和启动凋亡的相互作用。利用遗传修饰筛选，我们确定了四种Grim-Reaper诱导的细胞凋亡增强子，它们都调节泛素化过程：乌巴-1、skpA、fat facets（faf）和morgue。引人注目的是，morgueencode一个独特的蛋白质，包含一个F盒和一个泛素E2共轭结构域，缺乏泛素连接所需的活性位点Cys。在果蝇中，morgueactivity的减少抑制了grim-reaper诱导的细胞死亡。在培养的细胞中，Morgue诱导的凋亡被DIAP 1抑制。Morgue靶向表达下调果蝇组织中DIAP 1水平，Morgue和Rpr共同下调培养细胞中DIAP 1水平。与SCF泛素E3连接酶复合物中潜在的底物结合功能一致，Morgue表现出与SkpA的F盒依赖性关联和与DIAP 1的F盒独立性关联。因此，Morgue可能通过靶向DIAP 1进行泛素化和周转而在凋亡中发挥关键作用。
InDrosophila melanogaster, apoptosis is controlled by the integrated actions of the Grim-Reaper (Grim-Rpr) andDrosophilaInhibitor of Apoptosis (DIAP) proteins (reviewed in refs –). The anti-apoptotic DIAPs bind to caspases and inhibit their proteolytic activities. DIAPs also bind to Grim-Rpr proteins, an interaction that promotes caspase activity and the initiation of apoptosis. Using a genetic modifier screen, we identified four enhancers ofgrim-reaper-induced apoptosis that all regulate ubiquitination processes:uba-1,skpA,fat facets(faf), andmorgue. Strikingly,morgueencodes a unique protein that contains both an F box and a ubiquitin E2 conjugase domain that lacks the active site Cys required for ubiquitin linkage. A reduction ofmorgueactivity suppressedgrim-reaper-induced cell death inDrosophila. In cultured cells, Morgue induced apoptosis that was suppressed by DIAP1. Targetedmorgueexpression downregulated DIAP1 levels inDrosophilatissue, and Morgue and Rpr together downregulated DIAP1 levels in cultured cells. Consistent with potential substrate binding functions in an SCF ubiquitin E3 ligase complex, Morgue exhibited F box-dependent association with SkpA and F box-independent association with DIAP1. Morgue may thus have a key function in apoptosis by targeting DIAP1 for ubiquitination and turnover.