The role of the WWC protein family in organ size control

WWC蛋白家族在器官大小控制中的作用

• 批准号: 274442024
• 负责人: Professor Dr. Michael Krahn, Ph.D.
• 金额: --
• 依托单位: Medizinische Klinik D: Allg. Innere Medizin und Notaufnahme sowie Nieren- und Hochdruckkrankheiten und Rheumatologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/274442024?language=en
• 关键词: role; WWC; protein; family; organ

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.

细胞增殖和适当的器官大小通过复杂的信号转导级联网络进行调节。在这种情况下，河马途径，其中包括受体分子，各种效应和激酶，履行了至关重要的作用，由于控制的细胞定位的共转录因子雅普和TAZ。核雅普和TAZ诱导特定靶基因的表达，这些靶基因激活细胞增殖，抑制凋亡，从而促进高等生物的器官生长。Kibra的异位过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的失调。Kibra如何在果蝇器官生长控制中发挥作用的分子机制主要是未解决的。在高等动物（例如哺乳动物）中，KIBRA（也称为WWC 1）是WWC蛋白家族的成员，该家族还包括高度相似的分子WWC 2和WWC 3。到目前为止，还不知道WWC蛋白在器官生长调节中的作用。在我们提出的项目中，使用复杂的生化分析方法和体外蛋白质-蛋白质结合研究结合两种动物模型（转基因果蝇和小鼠），我们希望阐明WWC蛋白通过河马途径调节器官生长的功能。