Regulation of nucleocytoplasmic transports by sumoylation

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在翻译后被转移到目标蛋白的赖氨酸残基上。SUMOylation反应是由酶级联反应介导的，该酶级联反应由激活酶E1、偶联酶E2和各种底物特异性E3连接酶组成。由于特定蛋白酶的活性，这是一个可逆的过程，它使SUMO脱离其目标。我们最近发现来自酿酒酵母（Saccharomyces cerevisiae）的Kap114是一种介导蛋白质输入细胞核的输入蛋白家族受体，可被SUMO修饰和调节。我们将SUMO描述为核内货物释放因子，除了kap114介导的进口途径所需的Ran GTPase之外。因此，SUMO在核胞质运输中起着迄今未知的作用，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以及sumo调节的核运输中其他因素的参与。此外，我们计划阐明SUMOylation循环组分本身的核孔复合物的转运机制。进一步的目标是找出是否和如何其他转运受体的输入β家族是由SUMOylation调节。我们的方法包括适当的蛋白质相互作用研究与纯化因子和定位研究的货物和受体分子使用野生型和突变株相结合。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信的功能意义。

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.