The E3 ubiquitin ligase NEDD4 is an LC3-interactive protein and regulates autophagy
The E3 ubiquitin ligase NEDD4 is an LC3-interactive protein and regulates autophagy
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E3 泛素连接酶 NEDD4 是一种 LC3 相互作用蛋白，可调节自噬
DOI：
10.1080/15548627.2016.1268301
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发表时间：
2017-01-01
期刊：
影响因子：
13.3
通讯作者：
Lin, Qiong
中科院分区：
文献类型：
--
作者：
Sun, Aiqin;Wei, Jing;Lin, Qiong
MAP 1 LC 3/LC 3家族在自噬体的生物发生和转运中起着重要作用。在这份报告中，我们表明，HECT家族E3泛素连接酶NEDD 4与LC 3相互作用，并参与自噬体的生物合成。NEDD 4通过C2和WW 2结构域之间区域中的保守WXXL LC 3结合基序与LC 3结合。敲低NEDD 4会削弱饥饿或雷帕霉素诱导的自噬和自噬体生物发生的激活，并导致与内质网膜标记物共定位的LC 3斑点聚集。电镜观察到NEDD 4敲除细胞中巨大的变形线粒体，表明NEDD 4可能在线粒体自噬中起作用。此外，SQSTM 1被NEDD 4泛素化，而LC 3作为NEDD 4连接酶活性的激活剂发挥作用。总而言之，我们的研究确定了NEDD 4在调节自噬中的重要作用。
The MAP1LC3/LC3 family plays an essential role in autophagosomal biogenesis and transport. In this report, we show that the HECT family E3 ubiquitin ligase NEDD4 interacts with LC3 and is involved in autophagosomal biogenesis. NEDD4 binds to LC3 through a conserved WXXL LC3-binding motif in a region between the C2 and the WW2 domains. Knockdown of NEDD4 impaired starvation-or rapamycin-induced activation of autophagy and autophagosomal biogenesis and caused aggregates of the LC3 puncta colocalized with endoplasmic reticulum membrane markers. Electron microscopy observed gigantic deformed mitochondria in NEDD4 knockdown cells, suggesting that NEDD4 might function in mitophagy. Furthermore, SQSTM1 is ubiquitinated by NEDD4 while LC3 functions as an activator of NEDD4 ligase activity. Taken together, our studies define an important role of NEDD4 in regulation of autophagy.