Pelisch Federico, Tammsalu Triin, Wang Bin, Jaffray Ellis G, Gartner Anton, Hay Ronald T
Centre for Gene Regulation and Expression, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
Centre for Gene Regulation and Expression, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
Mol Cell. 2017 Jan 5;65(1):66-77. doi: 10.1016/j.molcel.2016.11.001. Epub 2016 Dec 8.
During Caenorhabditis elegans oocyte meiosis, a multi-protein ring complex (RC) localized between homologous chromosomes, promotes chromosome congression through the action of the chromokinesin KLP-19. While some RC components are known, the mechanism of RC assembly has remained obscure. We show that SUMO E3 ligase GEI-17/PIAS is required for KLP-19 recruitment to the RC, and proteomic analysis identified KLP-19 as a SUMO substrate in vivo. In vitro analysis revealed that KLP-19 is efficiently sumoylated in a GEI-17-dependent manner, while GEI-17 undergoes extensive auto-sumoylation. GEI-17 and another RC component, the kinase BUB-1, contain functional SUMO interaction motifs (SIMs), allowing them to recruit SUMO modified proteins, including KLP-19, into the RC. Thus, dynamic SUMO modification and the presence of SIMs in RC components generate a SUMO-SIM network that facilitates assembly of the RC. Our results highlight the importance of SUMO-SIM networks in regulating the assembly of dynamic protein complexes.
在秀丽隐杆线虫卵母细胞减数分裂过程中,一种位于同源染色体之间的多蛋白环复合物(RC)通过染色体驱动蛋白KLP-19的作用促进染色体汇聚。虽然已知一些RC成分,但RC组装的机制仍不清楚。我们发现SUMO E3连接酶GEI-17/PIAS是KLP-19招募到RC所必需的,蛋白质组学分析确定KLP-19在体内是一种SUMO底物。体外分析表明,KLP-19以GEI-17依赖的方式有效地被SUMO化,而GEI-17则经历广泛的自身SUMO化。GEI-17和另一个RC成分,激酶BUB-1,含有功能性SUMO相互作用基序(SIMs),使它们能够将包括KLP-19在内的SUMO修饰蛋白招募到RC中。因此,动态SUMO修饰以及RC成分中SIMs的存在产生了一个SUMO-SIM网络,促进了RC的组装。我们的结果突出了SUMO-SIM网络在调节动态蛋白复合物组装中的重要性。