Universität zu Köln

Kondylis, Vangelis ORCID: 0000-0002-6970-8731, Polykratis, Apostolos, Ehlken, Hanno, Ochoa-Callejero, Laura ORCID: 0000-0001-5366-6613, Straub, Beate Katharina, Krishna-Subramanian, Santosh, Van, Trieu-My, Curth, Harald-Morten, Heise, Nicole, Weih, Falk, Klein, Ulf, Schirmacher, Peter, Kelliher, Michelle and Pasparakis, Manolis ORCID: 0000-0002-9870-0966 (2015). NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma by Inhibiting RIPK1 Kinase Activity-Mediated Hepatocyte Apoptosis. Cancer Cell, 28 (5). S. 582 - 599. CAMBRIDGE: CELL PRESS. ISSN 1878-3686

Full text not available from this repository.

Abstract

I kappa B kinase/necrosis factor kappa B (IKK/NF-kappa B) signaling exhibits important yet opposing functions in hepatocarcinogenesis. Mice lacking NEMO in liver parenchymal cells (LPC) spontaneously develop steatohepatitis and hepatocellular carcinoma (HOC) suggesting that NF-kappa B prevents liver disease and cancer. Here, we show that complete NF-kappa B inhibition by combined LPC-specific ablation of RelA, c-Rel, and RelB did not phenocopy NEMO deficiency, but constitutively active IKK2-mediated NF-kappa B activation prevented hepatocellular damage and HCC in NEMOLPC-KO mice. Knock-in expression of kinase inactive receptor-interacting protein kinase 1 (RIPK1) prevented hepatocyte apoptosis and HCC, while RIPK1 ablation induced TNFR1-associated death domain protein (TRADD)-dependent hepatocyte apoptosis and liver tumors in NEMOLPC-KO mice, revealing distinct kinase-dependent and scaffolding functions of RIPK1. Collectively, these results show that NEMO prevents hepatocarcinogenesis by inhibiting RIPK1 kinase activity-driven hepatocyte apoptosis through NF-kappa B-dependent and -independent functions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kondylis, Vangelis UNSPECIFIED orcid.org/0000-0002-6970-8731 UNSPECIFIED Polykratis, Apostolos UNSPECIFIED UNSPECIFIED UNSPECIFIED Ehlken, Hanno UNSPECIFIED UNSPECIFIED UNSPECIFIED Ochoa-Callejero, Laura UNSPECIFIED orcid.org/0000-0001-5366-6613 UNSPECIFIED Straub, Beate Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Krishna-Subramanian, Santosh UNSPECIFIED UNSPECIFIED UNSPECIFIED Van, Trieu-My UNSPECIFIED UNSPECIFIED UNSPECIFIED Curth, Harald-Morten UNSPECIFIED UNSPECIFIED UNSPECIFIED Heise, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Weih, Falk UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Ulf UNSPECIFIED UNSPECIFIED UNSPECIFIED Schirmacher, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Kelliher, Michelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-387174
DOI:	10.1016/j.ccell.2015.10.001
Journal or Publication Title:	Cancer Cell
Volume:	28
Number:	5
Page Range:	S. 582 - 599
Date:	2015
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1878-3686
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; NECROSIS-FACTOR RECEPTOR; TNF-INDUCED NECROPTOSIS; CELL-DEATH; MICE; GAMMA; HEPATOCARCINOGENESIS; PROLIFERATION; HOMEOSTASIS; EXPRESSION Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/38717