The role of the WWC protein family in organ size control

• Applicants: Professor Michael Krahn, Ph.D.; Privatdozent Dr. Joachim Kremerskothen; Dr. Dirk Oliver Wennmann
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 274442024

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.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Hermann Pavenstädt