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Targeted peptidecentric proteomics reveals caspase-7 as a substrate of the caspase-1 inflammasomes

Mohamed Lamkanfi UGent, Thirumala-Devi Kanneganti, Petra Van Damme UGent, Tom Vanden Berghe UGent, Isabel Vanoverberghe UGent, Joël Vandekerckhove, Peter Vandenabeele UGent, Kris Gevaert UGent and Gabriel Nuñez (2008) MOLECULAR & CELLULAR PROTEOMICS. 7(12). p.2350-2363
abstract
The aspartate-specific cysteine protease caspase-1 is activated by the inflammasomes and is responsible for the proteolytic maturation of the cytokines IL-1 beta and IL-18 during infection and inflammation. To discover new caspase-1 substrates, we made use of a proteome-wide gel-free differential peptide sorting methodology that allows unambiguous localization of the processing site in addition to identification of the substrate. Of the 1022 proteins that were identified, 20 were found to be specifically cleaved after Asp in the setup incubated with recombinant caspase-1. Interestingly, caspase-7 emerged as one of the identified caspase-1 substrates. Moreover half of the other identified cleavage events occurred at sites closely resembling the consensus caspase-7 recognition sequence DEVD, suggesting caspase-1-mediated activation of endogenous caspase-7 in this setup. Consistently recombinant caspase-1 cleaved caspase-7 at the canonical activation sites Asp(23) and Asp(198), and recombinant caspase-7 processed a subset of the identified substrates. In vivo, caspase-7 activation was observed in conditions known to induce activation of caspase-1, including Salmonella infection and microbial stimuli combined with ATP. Interestingly Salmonella-and lipopolysaccharide + ATP-induced activation of caspase-7 was abolished in macrophages deficient in caspase-1, the pattern recognition receptors Ipaf and Cryopyrin, and the inflammasome adaptor ASC, demonstrating an upstream role for the caspase-1 inflammasomes in caspase-7 activation in vivo. In contrast, caspase-1 and the inflammasomes were not required for caspase-3 activation. In conclusion, we identified 20 new substrates activated downstream of caspase-1 and validated caspase-1-mediated caspase-7 activation in vitro and in knock-out macrophages. These results demonstrate for the first time the existence of a nucleotide binding and oligomerization domain-like receptor/caspase-1/caspase-7 cascade and the existence of distinct activation mechanisms for caspase-3 and -7 in response to microbial stimuli and bacterial infection.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
INDUCED-PROXIMITY MODEL, INTERLEUKIN-1-BETA CONVERTING-ENZYME, N-TERMINAL PEPTIDES, MASS-SPECTROMETRY, MICE DEFICIENT, KEY MEDIATORS, ACTIVATION, APOPTOSIS, IDENTIFICATION, IPAF
journal title
MOLECULAR & CELLULAR PROTEOMICS
Mol. Cell. Proteomics
volume
7
issue
12
pages
2350 - 2363
Web of Science type
Article
Web of Science id
000261328200005
JCR category
BIOCHEMICAL RESEARCH METHODS
JCR impact factor
8.834 (2008)
JCR rank
4/65 (2008)
JCR quartile
1 (2008)
ISSN
1535-9476
DOI
10.1074/mcp.M800132-MCP200
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
445566
handle
http://hdl.handle.net/1854/LU-445566
date created
2009-01-02 09:48:00
date last changed
2016-12-19 15:44:16
@article{445566,
  abstract     = {The aspartate-specific cysteine protease caspase-1 is activated by the inflammasomes and is responsible for the proteolytic maturation of the cytokines IL-1 beta and IL-18 during infection and inflammation. To discover new caspase-1 substrates, we made use of a proteome-wide gel-free differential peptide sorting methodology that allows unambiguous localization of the processing site in addition to identification of the substrate. Of the 1022 proteins that were identified, 20 were found to be specifically cleaved after Asp in the setup incubated with recombinant caspase-1. Interestingly, caspase-7 emerged as one of the identified caspase-1 substrates. Moreover half of the other identified cleavage events occurred at sites closely resembling the consensus caspase-7 recognition sequence DEVD, suggesting caspase-1-mediated activation of endogenous caspase-7 in this setup. Consistently recombinant caspase-1 cleaved caspase-7 at the canonical activation sites Asp(23) and Asp(198), and recombinant caspase-7 processed a subset of the identified substrates. In vivo, caspase-7 activation was observed in conditions known to induce activation of caspase-1, including Salmonella infection and microbial stimuli combined with ATP. Interestingly Salmonella-and lipopolysaccharide + ATP-induced activation of caspase-7 was abolished in macrophages deficient in caspase-1, the pattern recognition receptors Ipaf and Cryopyrin, and the inflammasome adaptor ASC, demonstrating an upstream role for the caspase-1 inflammasomes in caspase-7 activation in vivo. In contrast, caspase-1 and the inflammasomes were not required for caspase-3 activation. In conclusion, we identified 20 new substrates activated downstream of caspase-1 and validated caspase-1-mediated caspase-7 activation in vitro and in knock-out macrophages. These results demonstrate for the first time the existence of a nucleotide binding and oligomerization domain-like receptor/caspase-1/caspase-7 cascade and the existence of distinct activation mechanisms for caspase-3 and -7 in response to microbial stimuli and bacterial infection.},
  author       = {Lamkanfi, Mohamed and Kanneganti, Thirumala-Devi and Van Damme, Petra and Vanden Berghe, Tom and Vanoverberghe, Isabel and Vandekerckhove, Jo{\"e}l and Vandenabeele, Peter and Gevaert, Kris and Nu{\~n}ez, Gabriel},
  issn         = {1535-9476},
  journal      = {MOLECULAR \& CELLULAR PROTEOMICS},
  keyword      = {INDUCED-PROXIMITY MODEL,INTERLEUKIN-1-BETA CONVERTING-ENZYME,N-TERMINAL PEPTIDES,MASS-SPECTROMETRY,MICE DEFICIENT,KEY MEDIATORS,ACTIVATION,APOPTOSIS,IDENTIFICATION,IPAF},
  language     = {eng},
  number       = {12},
  pages        = {2350--2363},
  title        = {Targeted peptidecentric proteomics reveals caspase-7 as a substrate of the caspase-1 inflammasomes},
  url          = {http://dx.doi.org/10.1074/mcp.M800132-MCP200},
  volume       = {7},
  year         = {2008},
}

Chicago
Lamkanfi, Mohamed, Thirumala-Devi Kanneganti, Petra Van Damme, Tom Vanden Berghe, Isabel Vanoverberghe, Joël Vandekerckhove, Peter Vandenabeele, Kris Gevaert, and Gabriel Nuñez. 2008. “Targeted Peptidecentric Proteomics Reveals Caspase-7 as a Substrate of the Caspase-1 Inflammasomes.” Molecular & Cellular Proteomics 7 (12): 2350–2363.
APA
Lamkanfi, M., Kanneganti, T.-D., Van Damme, P., Vanden Berghe, T., Vanoverberghe, I., Vandekerckhove, J., Vandenabeele, P., et al. (2008). Targeted peptidecentric proteomics reveals caspase-7 as a substrate of the caspase-1 inflammasomes. MOLECULAR & CELLULAR PROTEOMICS, 7(12), 2350–2363.
Vancouver
1.
Lamkanfi M, Kanneganti T-D, Van Damme P, Vanden Berghe T, Vanoverberghe I, Vandekerckhove J, et al. Targeted peptidecentric proteomics reveals caspase-7 as a substrate of the caspase-1 inflammasomes. MOLECULAR & CELLULAR PROTEOMICS. 2008;7(12):2350–63.
MLA
Lamkanfi, Mohamed, Thirumala-Devi Kanneganti, Petra Van Damme, et al. “Targeted Peptidecentric Proteomics Reveals Caspase-7 as a Substrate of the Caspase-1 Inflammasomes.” MOLECULAR & CELLULAR PROTEOMICS 7.12 (2008): 2350–2363. Print.