Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes.
Adaptor Proteins, Signal Transducing
/ metabolism
Animals
Antigens, Bacterial
/ metabolism
Apoptosis Regulatory Proteins
/ metabolism
Bacillus anthracis
/ enzymology
Bacterial Proteins
/ metabolism
Bacterial Toxins
/ metabolism
CARD Signaling Adaptor Proteins
/ chemistry
Caspase 1
/ metabolism
Death Domain Receptor Signaling Adaptor Proteins
/ chemistry
Enzyme Activation
HEK293 Cells
Host-Pathogen Interactions
/ immunology
Humans
Immunity, Innate
Inflammasomes
/ immunology
Mice
Mice, Inbred C57BL
NLR Proteins
Neoplasm Proteins
/ chemistry
Peptide Hydrolases
/ metabolism
Proteasome Endopeptidase Complex
/ metabolism
Protein Domains
Protein Subunits
Proteolysis
RAW 264.7 Cells
Shigella flexneri
/ enzymology
Ubiquitin-Protein Ligases
/ metabolism
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
05 04 2019
05 04 2019
Historique:
received:
09
05
2018
revised:
05
11
2018
accepted:
05
03
2019
pubmed:
16
3
2019
medline:
21
6
2019
entrez:
16
3
2019
Statut:
ppublish
Résumé
Inflammasomes are multiprotein platforms that initiate innate immunity by recruitment and activation of caspase-1. The NLRP1B inflammasome is activated upon direct cleavage by the anthrax lethal toxin protease. However, the mechanism by which cleavage results in NLRP1B activation is unknown. In this study, we find that cleavage results in proteasome-mediated degradation of the amino-terminal domains of NLRP1B, liberating a carboxyl-terminal fragment that is a potent caspase-1 activator. Proteasome-mediated degradation of NLRP1B is both necessary and sufficient for NLRP1B activation. Consistent with our functional degradation model, we identify IpaH7.8, a
Identifiants
pubmed: 30872533
pii: science.aau1330
doi: 10.1126/science.aau1330
pmc: PMC6532986
mid: NIHMS1026604
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Antigens, Bacterial
0
Apoptosis Regulatory Proteins
0
Bacterial Proteins
0
Bacterial Toxins
0
CARD Signaling Adaptor Proteins
0
CARD8 protein, human
0
Death Domain Receptor Signaling Adaptor Proteins
0
Inflammasomes
0
NLR Proteins
0
NLRP1 protein, human
0
Neoplasm Proteins
0
PIDD1 protein, human
0
Protein Subunits
0
anthrax toxin
0
ipaH protein, Shigella flexneri
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Peptide Hydrolases
EC 3.4.-
Caspase 1
EC 3.4.22.36
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R37 AI075039
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI064285
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI155634
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI063302
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI064285
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI075039
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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