文章：

YAP与TAZ的核输入与核输出

Nuclear Import and Export of YAP and TAZ

原文发布日期：12 October 2023

DOI: 10.3390/cancers15204956

类型: Article

开放获取: 是

英文摘要：

Yes-associated Protein (YAP) and its paralog Transcriptional Coactivator with PDZ-binding Motif (TAZ) are major regulators of gene transcription/expression, primarily controlled by the Hippo pathway and the cytoskeleton. Integrating an array of chemical and mechanical signals, they impact growth, differentiation, and regeneration. Accordingly, they also play key roles in tumorigenesis and metastasis formation. Their activity is primarily regulated by their localization, that is, Hippo pathway- and/or cytoskeleton-controlled cytosolic or nuclear sequestration. While many details of such prevailingretention modelshave been elucidated, much less is known about their actual nuclear traffic: import and export. Although their size is not far from the cutoff for passive diffusion through the nuclear pore complex (NPC), and they do not contain any classic nuclear localization (NLS) or nuclear export signal (NES), evidence has been accumulating that their shuttling involves mediated and thus regulatable/targetable processes. The aim of this review is to summarize emerging information/concepts about their nucleocytoplasmic shuttling, encompassing the relevant structural requirements (NLS, NES), nuclear transport receptors (NTRs, karyophererins), and NPC components, along with the potential transport mechanisms and their regulation. While dissecting retention vs. transport is often challenging, the emerging picture suggests that YAP/TAZ shuttles across the NPC via multiple, non-exclusive, mediated mechanisms, constituting a novel and intriguing facet of YAP/TAZ biology.

摘要翻译： 

Yes-associated Protein (YAP)及其旁系同源物Transcriptional Coactivator with PDZ-binding Motif (TAZ)是基因转录/表达的主要调控因子，主要受Hippo通路和细胞骨架调控。它们整合一系列化学与机械信号，影响生长、分化和再生过程，因此在肿瘤发生和转移形成中发挥关键作用。其活性主要受亚细胞定位调控，即通过Hippo通路和/或细胞骨架介导的胞质滞留或核内隔离。虽然此类主流滞留模型的诸多细节已被阐明，但关于其实际核转运过程（即核输入与输出）的认知仍较为有限。尽管YAP/TAZ的分子尺寸未显著超过核孔复合体（NPC）被动扩散的截留阈值，且不包含经典核定位信号（NLS）或核输出信号（NES），但越来越多的证据表明其核质穿梭涉及介导性、可调控/可靶向的转运过程。本综述旨在系统总结关于YAP/TAZ核质穿梭的新兴研究进展，涵盖相关结构特征（NLS/NES）、核转运受体（NTRs/核转运蛋白）及NPC组分，并探讨潜在转运机制及其调控方式。尽管区分滞留与转运机制常具挑战性，现有研究提示YAP/TAZ可能通过多种非排他性的介导机制穿越NPC，这构成了YAP/TAZ生物学中新颖而引人入胜的研究维度。

原文链接：

Nuclear Import and Export of YAP and TAZ