Send to

Choose Destination

See 1 citation found by title matching your search:

J Biol Chem. 2012 Oct 5;287(41):33983-95. doi: 10.1074/jbc.M112.384552. Epub 2012 Jul 23.

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

Author information

Department for Molecular Biomedical Research, Flanders Institute for Biotechnology (VIB), Ghent University, B-9052 Ghent (Zwijnaarde), Belgium.


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↓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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center