Department of Molecular Cell Biology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
Institute of Molecular Biology gGmbH, Ackermannweg 4, Mainz, 55128, Germany.
Nat Commun. 2018 Mar 16;9(1):1119. doi: 10.1038/s41467-018-03486-4.
Signal transduction by small ubiquitin-like modifier (SUMO) regulates a myriad of nuclear processes. Here we report on the role of SUMO in mitosis in human cell lines. Knocking down the SUMO conjugation machinery results in a delay in mitosis and defects in mitotic chromosome separation. Searching for relevant SUMOylated proteins in mitosis, we identify the anaphase-promoting complex/cyclosome (APC/C), a master regulator of metaphase to anaphase transition. The APC4 subunit is the major SUMO target in the complex, containing SUMO acceptor lysines at positions 772 and 798. SUMOylation is crucial for accurate progression of cells through mitosis and increases APC/C ubiquitylation activity toward a subset of its targets, including the newly identified target KIF18B. Combined, our findings demonstrate the importance of SUMO signal transduction for genome integrity during mitotic progression and reveal how SUMO and ubiquitin cooperate to drive mitosis.
小泛素样修饰物（SUMO）的信号转导调节着无数的核过程。在这里，我们报告 SUMO 在人细胞系有丝分裂中的作用。SUMO 连接酶的敲低导致有丝分裂延迟和有丝分裂染色体分离缺陷。在有丝分裂中寻找相关的 SUMO 化蛋白，我们鉴定出了后期促进复合物/周期蛋白（APC/C），这是从中期到后期过渡的主要调节剂。APC4 亚基是该复合物中的主要 SUMO 靶标，在位置 772 和 798 处含有 SUMO 接受赖氨酸。SUMO 化对于细胞准确地通过有丝分裂至关重要，并增加 APC/C 对其部分靶标的泛素化活性，包括新鉴定的靶标 KIF18B。综合来看，我们的发现表明 SUMO 信号转导在有丝分裂过程中对基因组完整性的重要性，并揭示了 SUMO 和泛素如何合作推动有丝分裂。
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