Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Institute of Biochemistry and Molecular Biology, College of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
FEBS J. 2021 Oct;288(19):5569-5585. doi: 10.1111/febs.15659. Epub 2020 Dec 19.
Extensive structural and functional studies have been carried out in the field of nucleocytoplasmic transport. Nuclear transport factors, such as Importin-α/-β, recognize nuclear localization signals (NLSs) on cargo, and together with the small GTPase Ran, facilitate their nuclear localization. However, it is now emerging that binding of nuclear transport factors to NLSs not only mediates nuclear transport but also contributes to a variety of cellular functions in eukaryotes. Here, we describe recent advances that reveal how NLSs facilitate diverse cellular functions beyond nuclear transport activity. We review separately NLS-mediated regulatory mechanisms at different levels of biological organization, including (a) assembly of higher-order structures; (b) cellular organelle dynamics; and (c) modulation of cellular stress responses and viral infections. Finally, we provide mechanistic insights into how NLSs can regulate such a broad range of functions via their structural and biochemical properties.
在核质转运领域已经进行了广泛的结构和功能研究。核转运因子，如 Importin-α/-β，识别货物上的核定位信号（NLS），并与小分子 GTPase Ran 一起促进其核定位。然而，现在出现的情况是，核转运因子与 NLS 的结合不仅介导核转运，而且有助于真核生物的各种细胞功能。在这里，我们描述了最近的进展，揭示了 NLS 如何促进核转运活性以外的各种细胞功能。我们分别综述了 NLS 在不同层次的生物组织中的调节机制，包括（a）高级结构的组装；（b）细胞细胞器动力学；和（c）细胞应激反应和病毒感染的调节。最后，我们提供了机制上的见解，说明 NLS 如何通过其结构和生化特性来调节如此广泛的功能。
