| Literature DB >> 28017612 |
Anne T Schneider1, Jérémie Gautheron1, Maria Feoktistova2, Christoph Roderburg3, Sven H Loosen3, Sanchari Roy3, Fabian Benz3, Peter Schemmer4, Markus W Büchler4, Ueli Nachbur5, Ulf P Neumann6, Rene Tolba7, Mark Luedde8, Jessica Zucman-Rossi9, Diana Panayotova-Dimitrova2, Martin Leverkus2, Christian Preisinger10, Frank Tacke3, Christian Trautwein3, Thomas Longerich11, Mihael Vucur12, Tom Luedde13.
Abstract
Receptor-interacting protein kinase 1 (RIPK1) represents an essential signaling node in cell death and inflammation. Ablation of Ripk1 in liver parenchymal cells (LPC) did not cause a spontaneous phenotype, but led to tumor necrosis factor (TNF)-dependent hepatocyte apoptosis and liver injury without affecting inducible nuclear factor κB (NF-κB) activation. Loss of Ripk1 induced the TNF-dependent proteasomal degradation of the E3-ligase, TNF receptor-associated factor 2 (TRAF2), in a kinase-independent manner, thereby activating caspase-8. Moreover, loss of both Ripk1 and Traf2 in LPC not only resulted in caspase-8 hyperactivation but also impaired NF-κB activation, promoting the spontaneous development of hepatocellular carcinoma. In line, low RIPK1 and TRAF2 expression in human HCCs was associated with an unfavorable prognosis, suggesting that RIPK1 collaborates with TRAF2 to inhibit murine and human hepatocarcinogenesis.Entities:
Keywords: HCC; NF-κB; RIP1; RIP3; RIPK3; apoptosis; cIAP-1; caspase-8; hepatocarcinogenesis; necroptosis
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Year: 2016 PMID： 28017612 DOI： 10.1016/j.ccell.2016.11.009
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743