SUMO targets the APC/C to regulate transition from metaphase to anaphase.

SUMO targets the APC/C to regulate transition from metaphase to anaphase.
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DOI:
10.1038/s41467-018-03486-4
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发表时间:
2018-03-16
影响因子:
16.6
通讯作者:
Vertegaal ACO
Vertegaal ACO
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Eifler K;Cuijpers SAG;Willemstein E;Raaijmakers JA;El Atmioui D;Ovaa H;Medema RH;Vertegaal ACO

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小泛素样修饰物(SUMO)的信号转导调节了无数的核过程。在这里,我们报告的作用,相扑在人类细胞系的有丝分裂。敲除SUMO接合机制导致有丝分裂延迟和有丝分裂染色体分离缺陷。寻找有丝分裂中相关的SUMO化蛋白,我们确定了后期促进复合物/细胞周期体(APC/C),一个中期到后期转换的主调节器。APC 4亚基是复合物中的主要SUMO靶标,在位置772和798处含有SUMO受体赖氨酸。SUMO化对于细胞通过有丝分裂的准确进展至关重要,并增加了APC/C对其靶点子集(包括新发现的靶点KIF 18 B)的遍在化活性。结合,我们的研究结果表明,在有丝分裂过程中的基因组完整性的SUMO信号转导的重要性,并揭示了SUMO和泛素如何合作,以推动有丝分裂。小泛素样修饰物(SUMO)的信号转导对细胞周期的进展很重要。在这里,作者表明SUMO化调节APC/C复合物,这是中期到后期过渡的主要协调者,对有丝分裂进程有影响。
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. Signal transduction by small ubiquitin-like modifier (SUMO) is important for cell cycle progression. Here the authors show that SUMOylation regulates the APC/C complex, a master orchestrator of metaphase to anaphase transition, with consequences for mitotic progression.
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