The Receptor Interacting Protein Kinases in the Liver

Seminars in Liver Disease
Lily Dara

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.

Citations

May 12, 2019·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Shaojun ShiLuc J W van der Laan
Jan 19, 2021·The Journal of Biological Chemistry·Andrea IorgaLily Dara
Dec 4, 2020·Cellular & Molecular Immunology·Hua WangYaron Rotman
Dec 24, 2020·International Journal of Molecular Sciences·Layla ShojaieLily Dara
Jul 6, 2021·European Journal of Clinical Investigation·Tawhidul IslamCecília M P Rodrigues

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