The role of the WWC protein family in organ size control

细胞增殖和适当的器官大小是通过一个复杂的信号转导级联网络调节的。在这种情况下，包含受体分子、各种效应物和激酶的hippo通路由于控制共转录因子YAP和TAZ的细胞定位而发挥了至关重要的作用。核YAP和TAZ诱导特定靶基因的表达，激活细胞增殖，抑制细胞凋亡，从而促进高等生物器官生长。Kibra蛋白最近被确定为果蝇hippo通路的一个重要组成部分。Kibra的异位过度表达或其内源性表达的抑制导致眼睛或翅膀的解剖结构和大小失调。果蝇的分子机制，Kibra如何在器官生长控制中发挥作用，主要是未解之谜。在高等动物（如哺乳动物）中，KIBRA（也称为WWC1）是WWC蛋白家族的成员，该家族还包括高度相似的分子WWC2和WWC3。到目前为止，对WWC蛋白在器官生长调节中的作用尚不清楚。在我们提出的项目中，我们希望利用先进的生化分析方法和体外蛋白-蛋白结合研究，结合两种动物模型（转基因果蝇和小鼠），阐明WWC蛋白通过河马途径调节器官生长的功能。

Cell proliferation and proper organ size is regulated via a complex network of signal transduction cascades. In this context, the hippo pathway, which encompasses receptor molecules, various effectors and kinases, fulfills a crucial role due to the control of the cellular localization of the co-transcription factors YAP and TAZ. Nuclear YAP and TAZ induce the expression of specific target genes that activate cell proliferation, inhibit apoptosis and therefore facilitate organ growth in higher organisms.The Kibra protein was recently identified as an important component of the hippo pathway in Drosophila. An ectopic overexpression of Kibra or an inhibition of its endogenous expression leads to a dysregulation of the anatomy and size of eyes or wings. The molecular mechanism, how Kibra exerts its function within organ growth control in Drosophila is mainly unsolved. In higher animals (e.g. mammals), KIBRA (also called WWC1) is the member of the WWC protein family that also includes the highly similar molecules WWC2 and WWC3. So far, nothing is known about the role of the WWC proteins in the regulation of organ growth. In our proposed project, using sophisticated biochemical analysis approaches and in vitro protein-protein binding studies in combination with two animal models (transgenic Drosophila and mice), we want to elucidate the function of the WWC proteins for regulated organ growth via the hippo pathway.