Jin Lingyan, Williamson Adam, Banerjee Sudeep, Philipp Isabelle, Rape Michael
Department of Molecular and Cell Biology, 16 Barker Hall, University of California at Berkeley, Berkeley, CA 94720-3202, USA.
Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012.
The anaphase-promoting complex (APC/C) orchestrates progression through mitosis by decorating cell-cycle regulators with ubiquitin chains. To nucleate chains, the APC/C links ubiquitin to a lysine in substrates, but to elongate chains it modifies lysine residues in attached ubiquitin moieties. The mechanism enabling the APC/C, and ubiquitin ligases in general, to switch from lysine residues in substrates to specific ones in ubiquitin remains poorly understood. Here, we determine the topology and the mechanism of assembly for the ubiquitin chains mediating functions of the human APC/C. We find that the APC/C triggers substrate degradation by assembling K11-linked ubiquitin chains, the efficient formation of which depends on a surface of ubiquitin, the TEK-box. Strikingly, homologous TEK-boxes are found in APC/C substrates, where they facilitate chain nucleation. We propose that recognition of similar motifs in substrates and ubiquitin enables the APC/C to assemble ubiquitin chains with the specificity and efficiency required for tight cell-cycle control.
后期促进复合物（APC/C）通过用泛素链修饰细胞周期调节因子来协调有丝分裂进程。为了起始链的形成，APC/C将泛素连接到底物中的一个赖氨酸上，但为了延长链，它会修饰连接的泛素部分中的赖氨酸残基。使APC/C以及一般的泛素连接酶从底物中的赖氨酸残基切换到泛素中特定的赖氨酸残基的机制仍知之甚少。在这里，我们确定了介导人类APC/C功能的泛素链的拓扑结构和组装机制。我们发现，APC/C通过组装K11连接的泛素链来触发底物降解，其有效形成依赖于泛素的一个表面，即TEK框。令人惊讶的是，在APC/C底物中发现了同源的TEK框，它们在那里促进链的起始。我们提出，识别底物和泛素中相似的基序使APC/C能够以严格的细胞周期控制所需的特异性和效率组装泛素链。
