Different strategies by distinct Wnt-signaling pathways in activating a nuclear transcriptional response.
Different strategies by distinct Wnt-signaling pathways in activating a nuclear transcriptional response.
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DOI：
10.1016/bs.ctdb.2022.02.008
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发表时间：
2022
影响因子：
--
通讯作者：
Mlodzik, Marek
中科院分区：
文献类型：
--
作者：
Vuong, Linh T;Mlodzik, Marek
Wnt家族分泌的糖脂蛋白通过多种信号转导途径传递信号，对胚胎发育、器官发育和动态平衡是必不可少的。WNT-通路在所有后生动物中都是保守的和关键的。Wnt信号通路包括典型的Wnt/β-catenin通路和几个非典型的信号分支，其中Wnt-平面细胞极性(PCP)信号和Wnt/钙通路受到最多的关注和最深入的了解。有趣的是，所有的Wnt-通路都有一个核信号分支，也可以影响许多不依赖于其核转录调控的细胞过程。在发育和疾病中，规范的Wnt/β-catenin信号对核转录反应是最关键的，但是该途径的“商业末端”--β-catenin如何转移到细胞核，作为Tcf/Lef转录因子家族的共同激活因子的机制(S)仍然不清楚。在这里，我们讨论和比较关于各自的Wnt信号通路如何激活核转录反应的非常不同的策略。我们还重点介绍了一些最近关于β-连环蛋白如何通过IFT-A、动蛋白-2和微管依赖机制转移到细胞核的新见解，以及这一方面的经典WNT信号如何以纤毛独立的方式使用纤毛蛋白，在果蝇和哺乳动物细胞之间保守。
The Wnt family of secreted glycolipo-proteins signals through multiple signal transduction pathways and is essential for embryonic development and organ development and homeostasis. The Wnt-pathways are conserved and critical in all metazoans. Wnt signaling pathways comprise the canonical Wnt/β-catenin pathway and several non-canonical signaling branches, of which Wnt-Planar Cell Polarity (PCP) signaling and the Wnt/Calcium pathway have received the most attention and are best understood. nterestingly, all Wnt-pathways have a nuclear signaling branch and also can affect many cellular processes independent of its nuclear transcriptional regulation. Canonical Wnt/β-catenin signaling is the most critical for a nuclear transcriptional response, in both development and disease, yet the mechanism(s) on how the “business end” of the pathway, β-catenin, translocates to the nucleus to act as co-activator to the TCF/Lef transcription factor family still remains obscure. Here we discuss and compare the very different strategies on how the respective Wnt signaling pathways activate a nuclear transcriptional response. We also highlight some recent new insights into how β-catenin is translocated to the nucleus via an IFT-A, Kinesin-2, and microtubule dependent mechanism and how this aspect of canonical Wnt-signaling uses ciliary proteins in a cilium independent manner, conserved between Drosophila and mammalian cells.