MDA-9/syntenin interacts with ubiquitin via a novel ubiquitin-binding motif
MDA-9/syntenin interacts with ubiquitin via a novel ubiquitin-binding motif
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DOI：
10.1007/s11010-011-0750-4
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发表时间：
2011-06-01
影响因子：
4.3
通讯作者：
Hatakeyama, Shigetsugu
中科院分区：
文献类型：
--
作者：
Okumura, Fumihiko;Yoshida, Koichi;Hatakeyama, Shigetsugu
泛素化似乎涉及蛋白酶体依赖性蛋白水解和膜运输系统，包括胞吞作用和胞吐作用。在这项研究中，我们通过酵母双杂交系统使用修饰的泛素（其中赖氨酸 48 被精氨酸取代）将 MDA-9/syntenin 鉴定为一种新型泛素结合蛋白。据报道，MDA-9/syntenin 是一种膜相关蛋白，调节涉及内吞作用和细胞内转运的细胞过程。我们发现 MDA-9/syntenin 通过非共价键与泛素结合，并被共价泛素化。 MDA-9/syntenin 没有迄今为止报道的泛素结合基序，这表明 MDA-9/syntenin 通过一种新的结合基序与泛素发生物理相互作用。 MDA-9/syntenin 在细胞中稳定，表明 MDA-9/syntenin 的泛素结合或 MDA-9/syntenin 的泛素化与蛋白水解无关。此外，我们发现野生型MDA-9/syntenin的过表达可增强丝状伪足的形成，而缺乏PDZ结构域的MDA-9/syntenin则抑制丝状伪足的形成，表明MDA-9/syntenin通过与泛素相互作用在调节癌症转移和侵袭中发挥重要作用。
Ubiquitination appears to be involved in proteasome-dependent proteolysis and in the membrane trafficking system including endocytosis and exocytosis. In this study, we identified MDA-9/syntenin as a novel ubiquitin-binding protein by a yeast two-hybrid system using modified ubiquitin in which lysine 48 is substituted by arginine. It has been reported that MDA-9/syntenin is a membrane-associated protein and regulates a cellular process involving endocytosis and intracellular transport. We found that MDA-9/syntenin binds to ubiquitin by a non-covalent bond and is ubiquitinated covalently. MDA-9/syntenin has no ubiquitin-binding motifs that have so far been reported, suggesting that MDA-9/syntenin physically interacts with ubiquitin via a novel binding motif. MDA-9/syntenin is stable in the cell, suggesting that ubiquitin binding of MDA-9/syntenin or ubiquitination of MDA-9/syntenin is not related to proteolysis. Furthermore, we showed that overexpression of wild-type MDA-9/syntenin enhances formation of filopodia, whereas MDA-9/syntenin lacking the PDZ domain inhibits the formation of filopodia, suggesting that MDA-9/syntenin plays an important role via interaction with ubiquitin in the regulation of cancer metastasis and invasion.