Holding RIPK1 on the Ubiquitin Leash in TNFR1 Signaling

Nieves Peltzer; Maurice Darding; Henning Walczak

doi:10.1016/j.tcb.2016.01.006

Holding RIPK1 on the Ubiquitin Leash in TNFR1 Signaling

Trends Cell Biol. 2016 Jun;26(6):445-461. doi: 10.1016/j.tcb.2016.01.006. Epub 2016 Feb 11.

Authors

Nieves Peltzer¹, Maurice Darding¹, Henning Walczak²

Affiliations

¹ Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London WC1E 6BT, UK.
² Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London WC1E 6BT, UK. Electronic address: h.walczak@ucl.ac.uk.

PMID: 26877205
DOI: 10.1016/j.tcb.2016.01.006

Abstract

The kinase RIPK1 is an essential signaling node in various innate immune signaling pathways being most extensively studied in the TNFR1 signaling pathway. TNF signaling can result in different biological outcomes including gene activation and cell death induction in the form of apoptosis or necroptosis. RIPK1 is believed to be crucial for regulating the balance between these opposing outcomes. It is therefore not surprising that RIPK1 is highly regulated, most notably by phosphorylation, ubiquitination, and their respective reversals. In this review, we discuss the biological functions of RIPK1 within the context of TNFR1 signaling. Finally, we discuss recent advances in the knowledge on three ubiquitin E3 ligases that exert regulatory functions on RIPK1 signaling: cIAP1, cIAP2, and LUBAC.

Keywords: LUBAC; RIPK1; TNFR1; cIAP1/2; necroptosis; ubiquitination.

Publication types

Review

MeSH terms

Animals
Cell Death
Humans
Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
Receptors, Tumor Necrosis Factor, Type I / metabolism*
Signal Transduction*
Ubiquitin / metabolism*
Ubiquitin-Protein Ligases / metabolism

Substances

Receptors, Tumor Necrosis Factor, Type I
Ubiquitin
Ubiquitin-Protein Ligases
Receptor-Interacting Protein Serine-Threonine Kinases