Degradomics reveals that cleavage specificity profiles of caspase-2 and effector caspases are alike
- Author
- Magdalena Wejda (UGent) , Francis Impens (UGent) , Nozomi Takahashi (UGent) , Petra Van Damme (UGent) , Kris Gevaert (UGent) and Peter Vandenabeele (UGent)
- Organization
- Project
- 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
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-3053575
- MLA
- Wejda, Magdalena, et al. “Degradomics Reveals That Cleavage Specificity Profiles of Caspase-2 and Effector Caspases Are Alike.” JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 287, no. 41, 2012, pp. 33983–95, doi:10.1074/jbc.M112.384552.
- 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. https://doi.org/10.1074/jbc.M112.384552
- 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): 33983–95. https://doi.org/10.1074/jbc.M112.384552.
- 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. doi:10.1074/jbc.M112.384552.
- 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://doi.org/10.1074/jbc.M112.384552}}, volume = {{287}}, year = {{2012}}, }
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