Hippo信号通路在器官大小的控制和组织稳态的维持中起着重要的作用，该信号通路的异常与癌症的发生发展密切相关。Amot-NF2和WWC1-NF2复合物是Hippo信号通路上游的重要调节复合物，目前关于这两个复合物的结构基础及其在Hippo信号通路中的调节机制还有待进一步阐明。为了深入理解这两个复合物装配的结构基础和相关功能机制，我们将综合运用多学科交叉手段，研究以下三个方面的内容：NF2/Merlin自抑制构象的结构基础和调节机制；Amot-NF2二元复合物和WWC1-NF2二元复合物的结构与调节Hippo信号通路的分子机制；WWC1和其新结合蛋白X调节Hippo信号通路的作用机制。本项目将通过复合物结构的解析，揭示Amot-NF2、WWC1-NF2和WWC1-蛋白X复合物调节Hippo信号通路的分子机制，阐明这些复合物蛋白蛋白突变导致肿瘤的发生发展的作用机制。

Hippo signaling pathway plays an important role in the control of organ size andthe maintenance of tissue homeostasis. The Amot-NF2 and WWC1-NF2 complex is an important regulatory complex in the upstream of the Hippo signaling pathway. The assembly of these two complex and its mechanism in the Hippo signaling pathway remain to be elucidated. In order to understand the strunctural and functional mechanism of these complex, we will use multi-disciplinary research methods to study the three following parts: NF2/Merlin autoinhibitory structure and regulation mechanism; study the structure and regulation mechianism of Amot-NF2 and WWC1-NF2 binary complex; the mechanism of WWC1 in regulating Hippo signaling pathway through the new binding protein X. The research results of this project will elucidate the upstream regulation mechanism of Hippo signaling pathway, reveal the assembly of the Amot-NF2、WWC1-NF2 and WWC1-protein X complex and clarify the tumorigenesis and developmental process of cancer causing by mutation of the complex protein.