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Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death
- Source :
- Science (New York, N.Y.). 362(6418)
- Publication Year :
- 2018
-
Abstract
- Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment that controls pyroptosis in macrophages. GSDMD is processed via inflammasome-activated caspase-1 or -11. It is currently unknown whether macrophage GSDMD can be processed by other mechanisms. Here, we describe an additional pathway controlling GSDMD processing. The inhibition of TAK1 or IκB kinase (IKK) by the Yersinia effector protein YopJ elicits RIPK1- and caspase-8–dependent cleavage of GSDMD, which subsequently results in cell death. GSDMD processing also contributes to the NLRP3 inflammasome–dependent release of interleukin-1β (IL-1β). Thus, caspase-8 acts as a regulator of GSDMD-driven cell death. Furthermore, this study establishes the importance of TAK1 and IKK activity in the control of GSDMD cleavage and cytotoxicity.
- Subjects :
- 0301 basic medicine
Programmed cell death
Inflammasomes
Regulator
IκB kinase
Cleavage (embryo)
Caspase 8
Article
03 medical and health sciences
RIPK1
Mice
0302 clinical medicine
Bacterial Proteins
NLR Family, Pyrin Domain-Containing 3 Protein
Animals
Humans
Plague
Multidisciplinary
Cell Death
Chemistry
Effector
Pyroptosis
Intracellular Signaling Peptides and Proteins
Phosphate-Binding Proteins
MAP Kinase Kinase Kinases
Cell biology
I-kappa B Kinase
Mice, Inbred C57BL
030104 developmental biology
030220 oncology & carcinogenesis
Host-Pathogen Interactions
Proteolysis
Apoptosis Regulatory Proteins
Subjects
Details
- ISSN :
- 10959203
- Volume :
- 362
- Issue :
- 6418
- Database :
- OpenAIRE
- Journal :
- Science (New York, N.Y.)
- Accession number :
- edsair.doi.dedup.....d211c02f073b05269712ca1cd68463b2