A10 - The role of the different LUBAC components in TNF-induced cell death, inflammation, immunity and disease
Receptor-ligand-mediated signalling in cell death, inflammation and immunity is regulated by a fine-tuned system of post-translational modifications by phosphorylation, ubiquitination and their respective reversals. The linear ubiquitin chain assembly complex (LUBAC) modulates signalling via the tumour necrosis factor (TNF) – TNF receptor 1 (TNFR1) system. We found LUBAC and the linear ubiquitin chains it creates to be crucial for the different TNFR1 signalling outputs by enabling full gene activation and preventing cell death. These studies contributed to establishing cell death as a trigger of inflammation and inflammatory disease. In this project we aim to understand and further dissect the biochemistry and function of LUBAC and and its individual components in physiology and in various disease settings.
Jain, R., Zhao, K., Sheridan, J.M. Heinlein, M., Kupresanin, F., Abeysekera, W., Hall, C., Rickard, J., Bouillet, P., Walczak, H., Strasser, A., Silke, J. & Gray, D.H.D. (2021). Dual roles for LUBAC signaling in thymic epithelial cell development and survival. Cell Death & Differentiation.