Cell death and inflammation modulated by the ubiquitin E3 ligase activities within LUBAC in metabolic inflammation (A10)

• Subject Area: Immunology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 414786233

The linear ubiquitin chain assembly complex (LUBAC), composed of HOIL-1, HOIP and SHARPIN, mediates optimal NF-κB-dependent gene activation and prevents cell death upon TNF stimulation. Whereas HOIP is the linear-E3-catalytic subunit, HOIL-1 E3 ligase limits promiscuous HOIP activity. We found that HOIP deficiency in adipocytes induces, whilst HOIL-1 inactivation protects from, metabolic syndrome, indicating that LUBAC is a crucial regulator of metabolism. We will further study how LUBAC, and the signalling events it regulates, affect metabolic inflammation using a series of genetic and state-of-the-art omics analyses. This research may lead to the identification of means to improve the outcome of patients suffering from metabolic diseases.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1403: Cell Death in Immunity, Inflammation and Disease
• Applicant Institution: Universität zu Köln
• Project Heads: Dr. Maria de las Nieves Peltzer, Ph.D.; Professor Dr. Henning Walczak, Ph.D., until 12/2023