Staudinger Jeff L
Pharmacology and Toxicology, University of Kansas, Lawrence, KS, 66045, USA.
Adv Exp Med Biol. 2017;963:99-110. doi: 10.1007/978-3-319-50044-7_6.
The SUMO conjugation system regulates key cellular processes including cell growth, division, mitochondrial dynamics, and the maintenance of genome stability in eukaryotic cells. The ubiquitin conjugation system regulates the stability of a myriad of vital cellular proteins in a signal-dependent manner by targeting them for destruction via the proteasome-mediated degradation pathway. Recent research efforts have unveiled an evolutionarily conserved and fundamental molecular interface between the SUMO and ubiquitin systems. A coordinated and integrated interaction between these two pathways plays a key role in adapting the SUMO-related stress response to alterations in sub-cellular protein localization, specific protein recruitment strategies, and the regulation of stress-inducible protein stability. This chapter will describe the interconnected and interdependent role of the SUMO and ubiquitin systems in mediating DNA damage repair and the genesis and the resolution of inflammatory-related diseases such as cancer. New insights regarding the interdependence of these two important post-translational modifications with nuclear receptor superfamily members will also be highlighted.
SUMO缀合系统调节关键的细胞过程，包括真核细胞中的细胞生长、分裂、线粒体动力学以及基因组稳定性的维持。泛素缀合系统通过蛋白酶体介导的降解途径将众多重要的细胞蛋白靶向破坏，从而以信号依赖的方式调节它们的稳定性。最近的研究工作揭示了SUMO和泛素系统之间进化上保守且基本的分子界面。这两条途径之间协调且整合的相互作用在使SUMO相关应激反应适应亚细胞蛋白质定位的改变、特定蛋白质募集策略以及应激诱导蛋白稳定性的调节方面起着关键作用。本章将描述SUMO和泛素系统在介导DNA损伤修复以及癌症等炎症相关疾病的发生和解决中的相互联系和相互依存作用。还将强调这两种重要的翻译后修饰与核受体超家族成员相互依存关系的新见解。
