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Semin Liver Dis 2018; 38(01): 073-086
DOI: 10.1055/s-0038-1629924
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Receptor Interacting Protein Kinases in the Liver

Lily Dara
1   Research Center for Liver Disease, University of Southern California, Keck School of Medicine, Los Angeles, California
2   Division of GI/Liver, Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California
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Further Information

Publication History

Publication Date:
22 February 2018 (online)

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Abstract

The receptor interacting serine/threonine kinase1 and 3 (RIPK1, RIPK3) are regulators of cell death and survival. RIPK1 kinase activity is required for necroptosis and apoptosis, while its scaffolding function is necessary for survival. Although both proteins can mediate apoptosis, RIPK1 and RIPK3 are most well-known for their role in the execution of necroptosis via the mixed lineage domain like pseudokinase. Necroptosis is a caspase-independent regulated cell death program which was first described in cultured cells with unknown physiologic relevance in the liver. Many recent reports have suggested that RIPK1 and/or RIPK3 participate in liver disease pathogenesis and cell death. Notably, both proteins have been shown to mediate inflammation independent of cell death. Whether necroptosis occurs in hepatocytes, and how it is executed in the presence of an intact caspase machinery is controversial. In spite of this controversy, it is evident that RIPK1 and RIPK3 participate in many experimental liver disease models. Therefore, in addition to cell death signaling, their necroptosis-independent role warrants further examination.

Keywords

RIPK1 - RIPK3 - cell death - necroptosis - apoptosis

Financial Support

This work was supported by NIH grant K08DK109141(LD).


 

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