Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell. 2014 May 8;157(4):910-21. doi: 10.1016/j.cell.2014.03.037.
Posttranslational modification of cell-cycle regulators with ubiquitin chains is essential for eukaryotic cell division. Such chains can be connected through seven lysine residues or the amino terminus of ubiquitin, thereby allowing the assembly of eight homogenous and multiple mixed or branched conjugates. Although functions of homogenous chain types have been described, physiological roles of branched structures are unknown. Here, we report that the anaphase-promoting complex (APC/C) efficiently synthesizes branched conjugates that contain multiple blocks of K11-linked chains. Compared to homogenous chains, the branched conjugates assembled by the APC/C strongly enhance substrate recognition by the proteasome, thereby driving degradation of cell-cycle regulators during early mitosis. Our work, therefore, identifies an enzyme and substrates for modification with branched ubiquitin chains and points to an important role of these conjugates in providing an improved signal for proteasomal degradation.
泛素链对细胞周期调节剂的翻译后修饰对于真核细胞分裂至关重要。这些链可以通过七个赖氨酸残基或泛素的氨基末端连接，从而允许组装八个同质和多个混合或分支的缀合物。尽管已经描述了同质链类型的功能，但分支结构的生理作用尚不清楚。在这里，我们报告说，有丝分裂促进复合物（APC/C）有效地合成了包含多个 K11 连接链块的分支缀合物。与同质链相比，由 APC/C 组装的分支缀合物强烈增强了蛋白酶体对底物的识别，从而在早期有丝分裂过程中驱动细胞周期调节剂的降解。因此，我们的工作确定了一种酶和底物，用于用分支泛素链进行修饰，并指出这些缀合物在提供蛋白酶体降解的改进信号方面具有重要作用。
