中文摘要
Hippo信号通路能够协同调控细胞生长、增殖与凋亡,在生长控制和器官大小的发育决定中发挥重要作用,该通路活性异常可导致人类多种癌症的发生。Scalloped(Sd)与Yorkie(Yki)组成的转录复合体是Hippo信号通路下游最主要的效应因子,越来越多的证据显示,多种机制可以调节Yki的转录活性,但Sd的活性调节机制鲜有报道。通过蛋白组学方法,我们鉴定到Nerfin-1(Nfn1)为Sd新的结合蛋白,并发现Nfn1拮抗Sd/Yki复合体的活性。本项目将在细胞水平揭示Nfn1通过Sd调节Hippo通路活性的分子机制,建立Nfn1控制器官大小发育和肿瘤发生的动物模型,为人类癌症的诊疗提供有效的新策略。
英文摘要
The Hippo signaling pathway coordinated regulates cell growth, proliferation and apoptosis and plays a crucial role in growth control and organ size determination. Its dysfunction has been involved in the development of multiple cancers. Scalloped (Sd)/Yorkie (Yki) transcriptional complex is the major effector of the Hippo signaling pathway. Of this complex the Yki activity is known to be controlled by multiple mechanisms; however, the regulation of Sd activity is very limited. In our IP-MS assays we have identified Nerfin-1(Nfn1) as a novel associated protein of Sd and shown Nfn1 antagonized Sd/Yki activity in vitro and in vivo. Here we are planning to uncover the molecular mechanism by which how Nfn1 regulating Hippo signaling via Sd in cell culture systems, and provide animal models to define its functions in organ size control and tumorigenesis.
