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Regulation of nucleocytoplasmic transports by sumoylation

通过苏酰化调节核细胞质运输

基本信息

批准号：
235832271
负责人：
Professor Dr. Gabriel Schlenstedt
金额：
--
依托单位：
Fachrichtung Medizinische Biochemie und Molekularbiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/235832271?language=en
关键词：
Regulation nucleocytoplasmic transports sumoylation

项目摘要

The ubiquitin-like protein SUMO regulates a number of intracellular processes by altering the stability, conformation, binding activity, or localization of target proteins. SUMO is transferred posttranslationally to a lysine residue of the target protein. The SUMOylation reaction is mediated by an enzymatic cascade consisting of an activating enzyme E1, a conjugating enzyme E2, and various substrate-specific E3 ligases. This is a reversible process due to the activity of specific proteases, which cleave SUMO off its targets. We recently showed that Kap114 from Saccharomyces cerevisiae, a receptor of the importin beta family mediating protein import into the cell nucleus, is modified and regulated by SUMO. We characterized SUMO as an intranuclear cargo release factor that is in addition to the Ran GTPase required for the Kap114-mediated import pathway. Thus SUMO plays a hitherto unknown role in nucleocytoplasmic transport, which we aim to study in detail. We will particularly focus on the examination of the molecular mechanism of SUMO-induced cargo release and the involvement of additional factors in SUMO-regulated nuclear transport. Furthermore, we plan to elucidate the mechanisms of transport across the nuclear pore complexes of the SUMOylation cycle components themselves. A further goal is to find out if and how other transport receptors of the importin beta family are regulated by SUMOylation. Our methods include a combination of appropriate protein interaction studies with purified factors and localization studies of cargo and receptor molecules using wildtype and mutant strains. In our future studies, we aim to gain further insight into the functional significance of the SUMO modification for communication between the cell nucleus and the cytoplasm.

泛素样蛋白SUMO通过改变靶蛋白的稳定性、构象、结合活性或定位来调节许多细胞内过程。SUMO被后转至靶蛋白的赖氨酸残基。SUMO化反应由酶级联反应介导，该酶级联反应由活化酶E1、缀合酶E2和各种底物特异性E3连接酶组成。这是一个可逆的过程，由于特定的蛋白酶的活性，切割SUMO关闭其目标。我们最近发现，Kap114从酿酒酵母，一个受体的importin β家族介导的蛋白质输入到细胞核，修饰和调节SUMO。我们的特点SUMO作为一个核内货物释放因子，除了需要的Kap114介导的进口途径的Ran GTdR。因此，SUMO发挥了迄今为止未知的作用，核质运输，我们的目标是详细研究。我们将特别关注SUMO诱导的货物释放的分子机制的检查和SUMO调节的核运输中的其他因素的参与。此外，我们计划阐明SUMO化循环组件本身的跨核孔复合物的运输机制。进一步的目标是找出是否以及如何通过SUMO化调节importin β家族的其他转运受体。我们的方法包括适当的蛋白质相互作用的研究与纯化的因素和货物和受体分子使用野生型和突变株的定位研究相结合。在我们未来的研究中，我们的目标是进一步了解SUMO修饰对细胞核和细胞质之间通讯的功能意义。