CASP3 Research Reagents

CASP3 Background

The CASP3 encodes the caspase-3, one of the major executioner caspases ^[1] in the apoptotic signaling because of its role in coordinating the demolishment of cellular structures such as DNA fragmentation or membrane blebbing. Caspase-3 is produced as a zymogen in an inactive pro-form. Cleavage and activation of pro-caspase-3 are catalyzed by initiator caspases, caspase-8, and caspase-9 through an internal cleavage to separate the large and small subunits to generate the active caspase-3 heterodimer ^[2]. In the APAF-1/caspase-9 apoptosome-initiated caspase activation cascade, caspase-3 has been shown to mediate feedback processing on caspase-9 ^[3][4]. Once activated, caspase-3 cleaves Bcl-2 and Bcl-XL, which abolishes the anti-apoptotic function of these proteins and releases C-terminal fragments that are pro-apoptotic. The cleavage of ICAD (inhibitor of caspase-activated DNase) by caspase-3 prompts the release of active CAD, which cleaves DNA and promotes chromatin condensation ^[5]. Caspase-3 also cleaves and activates gelsolin, a protein that regulates actin dynamics. Activated gelsolin promotes both cytoplasmic and nuclear apoptosis ^[6]. Katelyn G. Ponder et al. proved an initial cleavage event at D9 is required to allow cleavage at D28 that causes the complete removal of the prodomain allowing for full caspase-3 activation ^[7].

[1] Boatright KM, Salvesen GS Mechanisms of caspase activation [J]. Curr Opin Cell Biol. 2003 Dec; 15(6):725-31.
[2] Zou, H., Henzel, et al. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3 [J]. Cell 90, 405-413 (1997).
[3] Slee EA, et al. Ordering the cytochrome c-initiated caspase cascade: Hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner [J]. J Cell Biol, 1999, 144:281-292.
[4] Srinivasula SM, Ahmad M, et al. Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization [J]. Mol Cell, 1998, 1:949-957.
[5] Enari, M. et al. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD [J]. Nature 391, 43-50 (1998).
[6] Cohen, G. M. Caspases: the executioners of apoptosis [J]. Biochem. J. 326(Pt 1), 1-16 (1997).
[7] Katelyn G. Ponder and Lawrence H. Boise The prodomain of caspase-3 regulates its own removal and caspase activation [J]. Cell Death Discovery volume 5, Article number: 56 (2019).