Mediated nuclear import and export of TAZ and the underlying molecular requirements.
Mediated nuclear import and export of TAZ and the underlying molecular requirements.
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DOI：
10.1038/s41467-018-07450-0
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发表时间：
2018-11-23
影响因子：
16.6
通讯作者：
Kapus A
中科院分区：
文献类型：
--
作者：
Kofler M;Speight P;Little D;Di Ciano-Oliveira C;Szászi K;Kapus A
雅普/TAZ的核质分布受Hippo通路和细胞骨架的调节。虽然与胞质和核“滞留因子”（14-3-3和TEAD）的相互作用已知控制其定位，但雅普/TAZ穿梭的基本方面仍不清楚。目前尚不清楚易位是否仅通过被动扩散或通过介导的转运发生，并且尚未确定潜在的核定位和外排信号（NLS，内斯）及其推定的调节。在这里，我们表明，TAZ循环是一个介导的过程，并确定潜在的NLS和内斯。的C-末端NLS，代表一类新的进口图案，是必要的和足够的有效的核摄取通过RAN独立的机制。RhoA活性直接刺激这种输入。内斯位于TEAD结合结构域内，可被TEAD掩蔽，从而阻止外排。因此，我们描述了一个RhoA调节的NLS，TEAD调节的内斯，并提出了一个改进的模型核质TAZ穿梭超越“保留”。转录辅因子雅普和TAZ通过其核质穿梭受Hippo信号传导和机械力调节。在这里，作者确定了RhoA调节的C-末端核定位信号和TEAD调节的N-末端核输出信号的TAZ在上皮细胞系。
Nucleocytoplasmic distribution of Yap/TAZ is regulated by the Hippo pathway and the cytoskeleton. While interactions with cytosolic and nuclear “retention factors” (14–3–3 and TEAD) are known to control their localization, fundamental aspects of Yap/TAZ shuttling remain undefined. It is unclear if translocation occurs only by passive diffusion or via mediated transport, and neither the potential nuclear localization and efflux signals (NLS, NES) nor their putative regulation have been identified. Here we show that TAZ cycling is a mediated process and identify the underlying NLS and NES. The C-terminal NLS, representing a new class of import motifs, is necessary and sufficient for efficient nuclear uptake via a RAN-independent mechanism. RhoA activity directly stimulates this import. The NES lies within the TEAD-binding domain and can be masked by TEAD, thereby preventing efflux. Thus, we describe a RhoA-regulated NLS, a TEAD-regulated NES and propose an improved model of nucleocytoplasmic TAZ shuttling beyond "retention". The transcriptional co-factors Yap and TAZ are regulated by Hippo signalling and mechanical forces via their nucleocytoplasmic shuttling. Here the authors identify a RhoA-regulated C-terminal nuclear localization signal and a TEAD-regulated N-terminal nuclear export signal of TAZ in an epithelial cell line.
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影响因子：
21.3
作者：
Lin KC;Moroishi T;Meng Z;Jeong HS;Plouffe SW;Sekido Y;Han J;Park HW;Guan KL
通讯作者：
Guan KL
影响因子：
64.5
作者：
Fornerod, M;Ohno, M;Mattaj, IW
通讯作者：
Mattaj, IW
影响因子：
14.8
作者：
Chan P;Han X;Zheng B;DeRan M;Yu J;Jarugumilli GK;Deng H;Pan D;Luo X;Wu X
通讯作者：
Wu X
影响因子：
--
作者：
Du, YH;Masters, SC;Fu, H
通讯作者：
Fu, H
影响因子：
9.2
作者：
Codelia, Veronica A.;Sun, Gongping;Irvine, Kenneth D.
通讯作者：
Irvine, Kenneth D.