Catalog Number:

RA15048

Product Type:

Affinity Purified

Immunogen Sequence:

Recombinant mouse Caspase-12, amino acids 1-419 with a carboxyl-terminal six histidine tag

Host:

Rabbit

Reactivity:

Rat, Mouse

Applications:

Western Blot

Description:

This enzyme is a member of a family of evolutionarily conserved cysteine protease proteins known as caspases . Many of these enzymes are part of a proteolytic cascade that plays a central role in cell death by apoptosis. TRAF-2 has been shown to couple ER stress sensors with activation of caspase-12 by interacting with procaspase-12 and promoting procaspase-12 activation (Yoneda et al). Caspase-7 has been shown to activate caspase-12 (Rao et al). Inactive caspase-12 can be activated also by cleavage with calpain (Nakagawa et al). Caspase-12 is localized to the endoplasmic reticulum and activated by perturbation of endoplasmic reticulum calcium homeostasis, hypoxia, glucose starvation, treatment of cells with ER stress inducers such as brefeldin-A or thapsigargin, and accumulation of excess proteins. Membrane- or mitochondrial-targeted signals of apoptosis do not activate caspase-12. Knock-out mice that that do not express caspase-12 are resistant to endoplasmic reticulum stress induced apoptosis , but their cells undergo apoptosis in response to other death stimuli. Cortical neurons of these mice are defective in apoptosis induced by amyloid-beta protein but not by staurosporine or trophic factor deprivation. ( Nakagawa et al). Bitko et al have demonstrated that apoptosis induced by infection with Respiratory Syncytial Virus in the lung epithelial cell line A549 occurs through an endoplasmic reticulum stress response that activates caspase-12, and that this response does not involve activation of transcription factor NF-kappa-B.

Reference:

Bitko V and Barik S An endoplasmic reticulum-specific stress-activated caspase (caspase-12) is implicated in the apoptosis of A549 epithelial cells by respiratory syncytial virus. Journal of Cellular Biochemistry 80(3): 441-54 (2001).

Nakagawa T and Yuan J Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. Journal of Cell Biology 150(4): 887-94 (2000).

Nakagawa T et al Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403(6765): 98-103 (2000).

Rao RV et al Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. Journal of Biological Chemistry 276(36): 33869-74 (2001).

Yoneda T et al Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. Journal of Biological Chemistry 276(17): 13935-40 (2001).