Advanced search
1 file | 1.91 MB Add to list

Degradomics reveals that cleavage specificity profiles of caspase-2 and effector caspases are alike

Magdalena Wejda (UGent) , Francis Impens (UGent) , Nozomi Takahashi (UGent) , Petra Van Damme (UGent) , Kris Gevaert (UGent) and Peter Vandenabeele (UGent)
(2012) JOURNAL OF BIOLOGICAL CHEMISTRY. 287(41). p.33983-33995
Author
Organization
Project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Abstract
Caspase-2 is considered an initiator caspase because its long prodomain contains a CARD domain that allows its recruitment and activation in several complexes by homotypic death domain-fold interactions. Because little is known about the function and specificity of caspase-2 and its physiological substrates, we compared the cleavage specificity profile of recombinant human caspase-2 with those of caspase-3 and -7 by analyzing cell lysates using N-terminal COmbined FRActional DIagonal Chromatography (COFRADIC). Substrate analysis of the 68 cleavage sites identified in 61 proteins revealed that the protease specificities of human caspases-2, -3, and -7 largely overlap, revealing the DEVD down arrow G consensus cleavage sequence. We confirmed that Asp(563) in eukaryotic translation initiation factor 4B (eIF4B) is a cleavage site preferred by caspase-2 not only in COFRADIC setup but also upon co-expression in HEK 293T cells. These results demonstrate that activated human caspase-2 shares remarkably overlapping protease specificity with the prototype apoptotic executioner caspases-3 and -7, suggesting that caspase-2 could function as a proapoptotic caspase once released from the activating complex.
Keywords
N-TERMINAL PEPTIDES, FRACTIONAL DIAGONAL CHROMATOGRAPHY, CYTOSOLIC PHOSPHOLIPASE A(2), FAS-INDUCED APOPTOSIS, CELL-DEATH, QUANTITATIVE PROTEOMICS, INFLAMMATORY CASPASES, GENOTOXIC STRESS, STRUCTURAL BASIS, DNA-DAMAGE

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 1.91 MB

Citation

Please use this url to cite or link to this publication:

MLA
Wejda, Magdalena, Francis Impens, Nozomi Takahashi, et al. “Degradomics Reveals That Cleavage Specificity Profiles of Caspase-2 and Effector Caspases Are Alike.” JOURNAL OF BIOLOGICAL CHEMISTRY 287.41 (2012): 33983–33995. Print.
APA
Wejda, M., Impens, F., Takahashi, N., Van Damme, P., Gevaert, K., & Vandenabeele, P. (2012). Degradomics reveals that cleavage specificity profiles of caspase-2 and effector caspases are alike. JOURNAL OF BIOLOGICAL CHEMISTRY, 287(41), 33983–33995.
Chicago author-date
Wejda, Magdalena, Francis Impens, Nozomi Takahashi, Petra Van Damme, Kris Gevaert, and Peter Vandenabeele. 2012. “Degradomics Reveals That Cleavage Specificity Profiles of Caspase-2 and Effector Caspases Are Alike.” Journal of Biological Chemistry 287 (41): 33983–33995.
Chicago author-date (all authors)
Wejda, Magdalena, Francis Impens, Nozomi Takahashi, Petra Van Damme, Kris Gevaert, and Peter Vandenabeele. 2012. “Degradomics Reveals That Cleavage Specificity Profiles of Caspase-2 and Effector Caspases Are Alike.” Journal of Biological Chemistry 287 (41): 33983–33995.
Vancouver
1.
Wejda M, Impens F, Takahashi N, Van Damme P, Gevaert K, Vandenabeele P. Degradomics reveals that cleavage specificity profiles of caspase-2 and effector caspases are alike. JOURNAL OF BIOLOGICAL CHEMISTRY. 2012;287(41):33983–95.
IEEE
[1]
M. Wejda, F. Impens, N. Takahashi, P. Van Damme, K. Gevaert, and P. Vandenabeele, “Degradomics reveals that cleavage specificity profiles of caspase-2 and effector caspases are alike,” JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 287, no. 41, pp. 33983–33995, 2012.
@article{3053575,
  abstract     = {Caspase-2 is considered an initiator caspase because its long prodomain contains a CARD domain that allows its recruitment and activation in several complexes by homotypic death domain-fold interactions. Because little is known about the function and specificity of caspase-2 and its physiological substrates, we compared the cleavage specificity profile of recombinant human caspase-2 with those of caspase-3 and -7 by analyzing cell lysates using N-terminal COmbined FRActional DIagonal Chromatography (COFRADIC). Substrate analysis of the 68 cleavage sites identified in 61 proteins revealed that the protease specificities of human caspases-2, -3, and -7 largely overlap, revealing the DEVD down arrow G consensus cleavage sequence. We confirmed that Asp(563) in eukaryotic translation initiation factor 4B (eIF4B) is a cleavage site preferred by caspase-2 not only in COFRADIC setup but also upon co-expression in HEK 293T cells. These results demonstrate that activated human caspase-2 shares remarkably overlapping protease specificity with the prototype apoptotic executioner caspases-3 and -7, suggesting that caspase-2 could function as a proapoptotic caspase once released from the activating complex.},
  author       = {Wejda, Magdalena and Impens, Francis and Takahashi, Nozomi and Van Damme, Petra and Gevaert, Kris and Vandenabeele, Peter},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keywords     = {N-TERMINAL PEPTIDES,FRACTIONAL DIAGONAL CHROMATOGRAPHY,CYTOSOLIC PHOSPHOLIPASE A(2),FAS-INDUCED APOPTOSIS,CELL-DEATH,QUANTITATIVE PROTEOMICS,INFLAMMATORY CASPASES,GENOTOXIC STRESS,STRUCTURAL BASIS,DNA-DAMAGE},
  language     = {eng},
  number       = {41},
  pages        = {33983--33995},
  title        = {Degradomics reveals that cleavage specificity profiles of caspase-2 and effector caspases are alike},
  url          = {http://dx.doi.org/10.1074/jbc.M112.384552},
  volume       = {287},
  year         = {2012},
}

Altmetric
View in Altmetric
Web of Science
Times cited: