Department of Biochemistry and Molecular Biology, Johns Hopkins University, Baltimore, United States.
Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States.
Elife. 2018 Mar 8;7:e29539. doi: 10.7554/eLife.29539.
The Anaphase Promoting Complex/Cyclosome (APC/C) is a ubiquitin E3 ligase that functions as the gatekeeper to mitotic exit. APC/C activity is controlled by an interplay of multiple pathways during mitosis, including the spindle assembly checkpoint (SAC), that are not yet fully understood. Here, we show that sumoylation of the APC4 subunit of the APC/C peaks during mitosis and is critical for timely APC/C activation and anaphase onset. We have also identified a functionally important SUMO interacting motif in the cullin-homology domain of APC2 located near the APC4 sumoylation sites and APC/C catalytic core. Our findings provide evidence of an important regulatory role for SUMO modification and binding in affecting APC/C activation and mitotic exit.
有丝分裂后期促进复合物/环体（APC/C）是一种泛素 E3 连接酶，作为有丝分裂退出的门控因子。APC/C 的活性受到有丝分裂过程中多种途径的相互作用的控制，包括纺锤体组装检查点（SAC），但这些途径尚未完全了解。在这里，我们表明 APC/C 的 APC4 亚基的 SUMO 化在有丝分裂期间达到峰值，对于 APC/C 的及时激活和后期起始至关重要。我们还在 APC2 的连接酶同源结构域中鉴定到一个位于 APC4 SUMO 化位点和 APC/C 催化核心附近的功能重要的 SUMO 相互作用基序。我们的发现提供了证据，证明 SUMO 修饰和结合在影响 APC/C 激活和有丝分裂退出方面发挥着重要的调节作用。
