Institute of Biotechnology, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, Texas 78245, USA.
J Biol Chem. 2010 Apr 2;285(14):10265-72. doi: 10.1074/jbc.M110.110551. Epub 2010 Feb 16.
Ufd2 is the founding member of E4 enzymes that are specifically involved in ubiquitin chain elongation but whose roles in proteolysis remain scarce. Here, using a genome-wide screen, we identified one cellular target of yeast Ufd2 as the membrane protein Pex29. The ubiquitin chains assembled on Pex29 in vivo by Ufd2 mainly contain Lys-48 linkages. We found that the ubiquitin-protein E3 ligase for overexpressed Pex29 is Doa10, which is known to be involved in protein quality control. Interestingly, not all Doa10 substrates are regulated by Ufd2, suggesting that E4 involvement is not specific to a particular E3, but may depend on the spatial arrangement of the E3-substrate interaction. Cells lacking UFD2 elicit an unfolded protein response, expanding the physiological function of Ufd2. Our results lead to novel insights into the biological role of Ufd2 and further underscore the significance of Ufd2 in proteolysis.
Ufd2 是 E4 酶的创始成员，专门参与泛素链延伸，但在蛋白水解中的作用仍然很少。在这里，我们使用全基因组筛选，鉴定出酵母 Ufd2 的一个细胞靶标是膜蛋白 Pex29。体内由 Ufd2 组装在 Pex29 上的泛素链主要含有 Lys-48 连接。我们发现，过表达 Pex29 的泛素蛋白 E3 连接酶是 Doa10，它已知参与蛋白质质量控制。有趣的是，并非所有的 Doa10 底物都受 Ufd2 调节，这表明 E4 的参与不是特定于特定的 E3，而是可能取决于 E3-底物相互作用的空间排列。缺乏 UFD2 的细胞会引发未折叠蛋白反应，扩大了 Ufd2 的生理功能。我们的结果为 Ufd2 的生物学作用提供了新的见解，并进一步强调了 Ufd2 在蛋白水解中的重要性。
