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Proteome-wide substrate analysis indicates substrate exclusion as a mechanism to generate caspase-7 versus caspase-3 specificity

Dieter Demon UGent, Petra Van Damme UGent, Tom Vanden Berghe UGent, Annelies Deceuninck UGent, Joost Van Durme UGent, Jelle Verspurten UGent, Kenny Helsens UGent, Francis Impens UGent, Magdalena Wejda UGent and Joost Schymkowitz, et al. (2009) MOLECULAR & CELLULAR PROTEOMICS. 8(12). p.2700-2714
abstract
Caspase-3 and -7 are considered functionally redundant proteases with similar proteolytic specificities. We performed a proteome-wide screen on a mouse macrophage lysate using the N-terminal combined fractional diagonal chromatography technology and identified 46 shared, three caspase-3-specific, and six caspase-7-specific cleavage sites. Further analysis of these cleavage sites and substitution mutation experiments revealed that for certain cleavage sites a lysine at the P5 position contributes to the discrimination between caspase-7 and -3 specificity. One of the caspase-7-specific substrates, the 40 S ribosomal protein S18, was studied in detail. The RPS18-derived P6-P5' undecapeptide retained complete specificity for caspase-7. The corresponding P6-P1 hexapeptide still displayed caspase-7 preference but lost strict specificity, suggesting that P' residues are additionally required for caspase-7-specific cleavage. Analysis of truncated peptide mutants revealed that in the case of RPS18 the P4-P1 residues constitute the core cleavage site but that P6, P5, P2', and P3' residues critically contribute to caspase-7 specificity. Interestingly, specific cleavage by caspase-7 relies on excluding recognition by caspase-3 and not on increasing binding for caspase-7.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
FORCE-FIELD, CELL-DEATH, APOPTOSIS, ACTIVATION, KEY MEDIATORS, FAMILY, IDENTIFICATION, N-TERMINAL PEPTIDES, KINETIC-ANALYSIS, PROTEOLYTIC CLEAVAGE SITES
journal title
MOLECULAR & CELLULAR PROTEOMICS
Mol. Cell. Proteomics
volume
8
issue
12
pages
15 pages
Web of Science type
Article
Web of Science id
000272711800008
JCR category
BIOCHEMICAL RESEARCH METHODS
JCR impact factor
8.791 (2009)
JCR rank
2/65 (2009)
JCR quartile
1 (2009)
ISSN
1535-9476
DOI
10.1074/mcp.M900310-MCP200
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
818070
handle
http://hdl.handle.net/1854/LU-818070
date created
2010-01-05 14:41:32
date last changed
2012-06-26 14:31:53
@article{818070,
  abstract     = {Caspase-3 and -7 are considered functionally redundant proteases with similar proteolytic specificities. We performed a proteome-wide screen on a mouse macrophage lysate using the N-terminal combined fractional diagonal chromatography technology and identified 46 shared, three caspase-3-specific, and six caspase-7-specific cleavage sites. Further analysis of these cleavage sites and substitution mutation experiments revealed that for certain cleavage sites a lysine at the P5 position contributes to the discrimination between caspase-7 and -3 specificity. One of the caspase-7-specific substrates, the 40 S ribosomal protein S18, was studied in detail. The RPS18-derived P6-P5' undecapeptide retained complete specificity for caspase-7. The corresponding P6-P1 hexapeptide still displayed caspase-7 preference but lost strict specificity, suggesting that P' residues are additionally required for caspase-7-specific cleavage. Analysis of truncated peptide mutants revealed that in the case of RPS18 the P4-P1 residues constitute the core cleavage site but that P6, P5, P2', and P3' residues critically contribute to caspase-7 specificity. Interestingly, specific cleavage by caspase-7 relies on excluding recognition by caspase-3 and not on increasing binding for caspase-7.},
  author       = {Demon, Dieter and Van Damme, Petra and Vanden Berghe, Tom and Deceuninck, Annelies and Van Durme, Joost and Verspurten, Jelle and Helsens, Kenny and Impens, Francis and Wejda, Magdalena and Schymkowitz, Joost and Rousseau, Frederic and Madder, Annemieke and Vandekerckhove, Jo{\"e}l and Declercq, Wim and Gevaert, Kris and Vandenabeele, Peter},
  issn         = {1535-9476},
  journal      = {MOLECULAR \& CELLULAR PROTEOMICS},
  keyword      = {FORCE-FIELD,CELL-DEATH,APOPTOSIS,ACTIVATION,KEY MEDIATORS,FAMILY,IDENTIFICATION,N-TERMINAL PEPTIDES,KINETIC-ANALYSIS,PROTEOLYTIC CLEAVAGE SITES},
  language     = {eng},
  number       = {12},
  pages        = {2700--2714},
  title        = {Proteome-wide substrate analysis indicates substrate exclusion as a mechanism to generate caspase-7 versus caspase-3 specificity},
  url          = {http://dx.doi.org/10.1074/mcp.M900310-MCP200},
  volume       = {8},
  year         = {2009},
}

Chicago
Demon, Dieter, Petra Van Damme, Tom Vanden Berghe, Annelies Deceuninck, Joost Van Durme, Jelle Verspurten, Kenny Helsens, et al. 2009. “Proteome-wide Substrate Analysis Indicates Substrate Exclusion as a Mechanism to Generate Caspase-7 Versus Caspase-3 Specificity.” Molecular & Cellular Proteomics 8 (12): 2700–2714.
APA
Demon, D., Van Damme, P., Vanden Berghe, T., Deceuninck, A., Van Durme, J., Verspurten, J., Helsens, K., et al. (2009). Proteome-wide substrate analysis indicates substrate exclusion as a mechanism to generate caspase-7 versus caspase-3 specificity. MOLECULAR & CELLULAR PROTEOMICS, 8(12), 2700–2714.
Vancouver
1.
Demon D, Van Damme P, Vanden Berghe T, Deceuninck A, Van Durme J, Verspurten J, et al. Proteome-wide substrate analysis indicates substrate exclusion as a mechanism to generate caspase-7 versus caspase-3 specificity. MOLECULAR & CELLULAR PROTEOMICS. 2009;8(12):2700–14.
MLA
Demon, Dieter, Petra Van Damme, Tom Vanden Berghe, et al. “Proteome-wide Substrate Analysis Indicates Substrate Exclusion as a Mechanism to Generate Caspase-7 Versus Caspase-3 Specificity.” MOLECULAR & CELLULAR PROTEOMICS 8.12 (2009): 2700–2714. Print.