Ubiquitination of phosphatidylethanolamine in organellar membranes
Ubiquitination of phosphatidylethanolamine in organellar membranes
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DOI：
10.1016/j.molcel.2022.08.008
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发表时间：
2022-10-06
期刊：
影响因子：
16
通讯作者：
Mizushima, Noboru
中科院分区：
文献类型：
--
作者：
Sakamaki, Jun-ichi;Ode, Koji L.;Mizushima, Noboru
泛素家族蛋白的共价结合是一种广泛存在的蛋白质翻译后修饰。在泛素家族中，ATG 8亚家族是例外的，因为它主要与磷脂缀合。然而，它仍然是未知的其他泛素家族蛋白质是否也结合到磷脂。在这里，我们报告泛素是共轭磷脂，主要是磷脂酰乙醇胺（PE），在酵母和哺乳动物细胞。泛素化的PE（Ub-PE）在内体和液泡（或溶酶体）中积累，并且其水平在饥饿期间增加。Ub-PE也存在于杆状病毒中。在酵母中，PE泛素化由经典泛素系统酶Uba 1（E1）、Ubc 4/5（E2）和Tul 1（E3）催化，并由Doa 4逆转。含有Ub-PE的脂质体在体外募集ESCRT组分Vps 27-Hse 1和Vps 23。泛素样NEDD 8和ISG 15也与磷脂缀合。这些发现表明与膜磷脂的缀合不是ATG 8特异性的，而是泛素家族的一般特征。
The covalent conjugation of ubiquitin family proteins is a widespread post-translational protein modification. In the ubiquitin family, the ATG8 subfamily is exceptional because it is conjugated mainly to phospholipids. However, it remains unknown whether other ubiquitin family proteins are also conjugated to phospholipids. Here, we report that ubiquitin is conjugated to phospholipids, mainly phosphatidylethanolamine (PE), in yeast and mammalian cells. Ubiquitinated PE (Ub-PE) accumulates at endosomes and the vacuole (or lysosomes), and its level increases during starvation. Ub-PE is also found in baculoviruses. In yeast, PE ubiquitination is catalyzed by the canonical ubiquitin system enzymes Uba1 (E1), Ubc4/5 (E2), and Tul1 (E3) and is reversed by Doa4. Liposomes containing Ub-PE recruit the ESCRT components Vps27-Hse1 and Vps23 in vitro. Ubiqui-tin-like NEDD8 and ISG15 are also conjugated to phospholipids. These findings suggest that the conjugation to membrane phospholipids is not specific to ATG8 but is a general feature of the ubiquitin family.