E3 ubiquitin ligase that recognizes sugar chains
E3 ubiquitin ligase that recognizes sugar chains
复制标题
DOI：
10.1038/nature00890
复制
发表时间：
2002-07-25
期刊：
影响因子：
64.8
通讯作者：
Tai, T
中科院分区：
文献类型：
--
作者：
Yoshida, Y;Chiba, T;Tai, T
内质网（ER）蛋白质的n -糖基化在蛋白质质量控制中起着核心作用（1-3）。在这里，我们报道了n -聚糖作为Skp1-Cullin1-Fbx2-Roc1 （SCFFbx2）泛素连接酶复合物降解的信号。F-box蛋白Fbx2（参考文献4）特异性结合到n -连接的高甘露糖低聚糖上的蛋白，随后促进n -糖基化蛋白的泛素化。预整合素β 1是Fbx2的靶标；这两种蛋白在抑制蛋白酶体后在细胞质中相互作用。此外，突变体Fbx2DeltaF缺乏形成SCF复合物所必需的F-box结构域，其表达明显阻碍了er相关降解途径中典型底物的降解（5,6）。我们的研究结果表明，SCFFbx2泛素化n -糖基化蛋白通过质量控制机制从内质网转移到细胞质。
N-glycosylation of proteins in the endoplasmic reticulum (ER) has a central role in protein quality control(1-3). Here we report that N-glycan serves as a signal for degradation by the Skp1-Cullin1-Fbx2-Roc1 (SCFFbx2) ubiquitin ligase complex. The F-box protein Fbx2 (ref. 4) binds specifically to proteins attached to N-linked high-mannose oligosaccharides and subsequently contributes to ubiquitination of N-glycosylated proteins. Pre-integrin beta1 is a target of Fbx2; these two proteins interact in the cytosol after inhibition of the proteasome. In addition, expression of the mutant Fbx2DeltaF, which lacks the F-box domain that is essential for forming the SCF complex, appreciably blocks degradation of typical substrates of the ER-associated degradation pathway(5,6). Our results indicate that SCFFbx2 ubiquitinates N-glycosylated proteins that are translocated from the ER to the cytosol by the quality control mechanism.