Die Rolle der Deubiquitinase CYLD für Leberschädigung und Hepatokarzinogenese
Hämatologie, Onkologie
Zellbiologie
Zusammenfassung der Projektergebnisse
This project aimed at dissecting the contribution of the deubiquitinating enzyme CYLD in the diseased liver. Our experiments shed light on unknown signaling events in liver parenchymal cells essentially contributing to fibrogenesis, cholangiocyte response to damage and carcinogenesis. During the regular funding period, we were able to conduct and perform experiments broadening the knowledge regarding (non-) canonical NFkB signaling in the liver and interactions with the deubiquitinase CYLD. In summary, the novelty of this project comprises the following highlights: i) In human chronic liver diseases, non-canonical NFkB and its master transcription factor RelB become activated and may be causatively involved in the progression of the disease. ii) RelB is able to drive and maintain biliary damage and fibrosis as shown in a mouse model. iii) Cholangiocytes can be activated by RelB into a secretory active and proliferative state. However, our study may harbor broad implications regarding the understanding of chronic liver diseases. This project reports for the first time a role of non-canonical NFkB signaling for cholangiopathies, chronic liver diseases and primary liver malignancies.
Projektbezogene Publikationen (Auswahl)
-
Nuclear expression of the deubiquitinase CYLD is associated with improved survival in human hepatocellular carcinoma. PLoS One. 2014 Oct 16;9(10):e110591
Welte S, Urbanik T, Elßner C, Kautz N, Koehler BC, Waldburger N, Bermejo JL, Pinna F, Weiss KH, Schemmer P, Jaeger D, Longerich T, Breuhahn K, Schulze-Bergkamen H
