RIP3: a molecular switch for necrosis and inflammation.
TLDR
The current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases is reviewed.Abstract:
The receptor-interacting protein kinase 3 (RIP3/RIPK3) has emerged as a critical regulator of programmed necrosis/ necroptosis, an inflammatory form of cell death with important functions in pathogen-induced and sterile inflammation. RIP3 activation is tightly regulated by phosphorylation, ubiquitination, and caspase-mediated cleavage. These post-translational modifications coordinately regulate the assembly of a macromolecular signaling complex termed the necrosome. Recently, several reports indicate that RIP3 can promote inflammation independent of its pronecrotic activity. Here, we review our current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases.read more
Citations
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Journal ArticleDOI
CYLD deubiquitinates RIP1 in the TNFα-induced necrosome to facilitate kinase activation and programmed necrosis.
TL;DR: The results suggest that CYLD controls RIP1 kinase activity during necrosome assembly, which could lead to reduced requirement for CYLD to remove ubiquitin chains from RIP1 in the TNFR-1 signaling complex.
Journal ArticleDOI
Programmed Necrosis in the Cross Talk of Cell Death and Inflammation
TL;DR: A unique signature illustrates the cooperative nature of necroptosis and innate inflammatory signaling pathways in managing cell and organismal stresses from pathogen infection and sterile tissue injury.
Journal ArticleDOI
Cutting Edge: RIPK1 Kinase Inactive Mice Are Viable and Protected from TNF-Induced Necroptosis In Vivo
Apostolos Polykratis,Nicole Hermance,Matija Zelic,Justine E. Roderick,Chun Kim,Trieu-My Van,Thomas H. Lee,Francis Ka-Ming Chan,Manolis Pasparakis,Michelle A. Kelliher +9 more
TL;DR: Genetic evidence is provided that the kinase activity of RIPK1 is not required for survival but is essential for TNF-, TRIF-, and viral-initiated necroptosis.
Journal ArticleDOI
Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death
Dan Weng,Robyn Marty-Roix,Sandhya Ganesan,Megan K. Proulx,Gregory I. Vladimer,William J. Kaiser,Edward S. Mocarski,Kimberly Lea Pouliot,Francis Ka-Ming Chan,Michelle A. Kelliher,Phillip A. Harris,John Bertin,Peter J. Gough,Dmitry M. Shayakhmetov,Jon D. Goguen,Katherine A. Fitzgerald,Neal S. Silverman,Egil Lien +17 more
TL;DR: It is proposed that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis challenge.
Journal ArticleDOI
Distinct roles of RIP1–RIP3 hetero- and RIP3–RIP3 homo-interaction in mediating necroptosis
Xiao-Nan Wu,Zhang-Hua Yang,Xin Wang,Yingying Zhang,Huilin Wan,Song Y,Xin Chen,Shao J,Jiahuai Han +8 more
TL;DR: It is proposed that the signaling events after the RIP1–RIP3 amyloid complex assembly are the recruitment of free RIP3 by the RIP3 in the amyloids scaffold followed by autophosphorylation of RIP3 and subsequent recruitment of MLKL by RIP3 to execute necroptosis.
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