Scientific background: |
Caspase 3 is a caspase protein which interacts with Survivin, XIAP, CFLAR, Caspase 8, HCLS1, Deleted in Colorectal Cancer, TRAF3 and GroEL. This gene which is located at 4q35 encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6, 7, and 9; and the protein itself is processed by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. And the caspase-3 activation in heart failure sequentially cleaves SRF and generates a truncated SRF that appears to function as a dominant-negative transcription factor. Additionally, the caspase-3 influence on bone mineral density should be considered in any in vivo application of caspase-3 inhibitors to the treatment of human disease. In erythroid precursors undergoing terminal differentiation, Hsp70 prevents active CASP3 from cleaving GATA1 and inducing apoptosis. |
References: |
1. Chang, J.; Wei, L.; Otani, T.; Youker, K. A.; Entman, M. L.; Schwartz, R. J. : Inhibitory cardiac transcription factor, SRF-N, is generated by caspase 3 cleavage in human heart failure and attenuated by ventricular unloading. Circulation 108: 407-413, 2003.
2. Miura, M.; Chen, X.-D.; Allen, M. R.; Bi, Y.; Gronthos, S.; Seo, B.-M.; Lakhani, S.; Flavell, R. A.; Feng, X.-H.; Robey, P. G.; Young, M.; Shi, S. : A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells. J. Clin. Invest. 114: 1704-1713, 2004.
3. Ribeil, J.-A.; Zermati, Y.; Vandekerckhove, J.; Cathelin, S.; Kersual, J.; Dussiot, M.; Coulon, S.; Moura, I. C.; Zeuner, A.; Kirkegaard-Sorensen, T.; Varet, B.; Solary, E.; Garrido, C.; Hermine, O. : Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1. Nature 445: 102-105, 2007. |