Caspases are essential mediators of programmed cell death and are needed for both the induction of apoptosis as well as for aiding the degradation of cellular structures. Initiator caspases (such as Caspase-9) sense and respond to various signals including intracellular stress or binding of the death receptor to external ligands. Upon dimerization, initiator caspases gets activated, which follows cleavage of downstream effector caspases for carrying out the apoptotic program. Caspase-9 is activated through its association with Apaf-1 (apoptotic protease-activating factor-1) apoptosome complex (1). While cleavage is not required for caspase-9 activity, in vivo studies have demonstrated cleavage during apoptosis through western blotting with caspase-9 antibodies (1). This suggests caspase-9 cleavage may be important for other events during apoptosis aside from regulating the protein’s enzymatic activity. While various theories exist, some research suggests cleaved caspase-9 can interact with other mediators of apoptosis such as XIAP to help regulate the cell death signaling network (1).
Since caspase-9 is such an important initiator enzyme for apoptosis, caspse-9 antibodies and assays measuring its proteolytic activity are essential tools for investigating mechanisms of cell death in various biological systems. One such early study used the caspase-9 antibody to examine the dynamic subcellular localization of caspase-9 during neuronal cell death (2). This study showed caspase-9 resides in the mitochondria but gets released and translocates to the nucleus (2). Cheng et al. used the caspase-9 antibody to monitor its cleavage/activation in colon xenograft tumors and their team identified promising new cancer treatment agents with ability efficiently induce apoptosis in colon cancer model (3). Similarly, researchers used caspase-9 antibody to help identify treatments to sensitize pancreatic carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (4). These studies have demonstrated the utility of caspase-9 antibodies to investigate basic mechanisms of apoptosis and also in the search for new and more effective cancer treatment options.
Novus Biologicals offers Caspase-9 reagents for your research needs including:
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