Caspase-2 is a highly conserved member of the caspase family involved in the initiation and execution of apoptosis. While its function is still poorly understood, caspase-2 is thought to be important for apoptosis in response to DNA damage, bacterial infection, or abnormal mitosis (1). Caspase-2 contains an N-terminal caspase recruitment domain, the large p19 subunit containing the active site, and the small C-terminal p12 subunit (1). In response to various apoptotic signals caspase-2 undergoes dimerization. Caspase-2 then promotes its own cleavage into the mature active form consisting of a p19/p12 heterodimer (1).This active/cleaved form of caspase-2 can then cleave and activate pro-apoptotic signaling proteins such as the BCL-2 family protein BID (2). This promotes the release of cytochrome c and the induction of apoptosis (2). BID cleavage by caspase-2 was demonstrated by researchers at the University of California San Francisco (3). They measured caspase-2 levels through western blotting with a caspase-2 antibody and showed siRNA targeting caspase-2 disrupted BID cleavage downstream of ER stress (2). In addition to BID, various proteins have been identified as caspase-2 substrates. For example, golgin-160 is Golgi membrane protein whose cleavage by caspase-2 contributes to fragmentation of the Golgi during apoptosis (2).
The cleavage and activation of caspase-2 can be monitored through western blotting with caspase-2 antibodies specific to the active/cleaved form of caspase-2. Additionally, these caspase-2 antibodies can be used for immunofluorescence or cell fractionation to investigate caspase-2 processing within the cell upon cellular stress. The Samuels group at the New York University School of Medicine used the cell fractionation technique and western blotting with caspase-2 antibody to demonstrate that caspase-2 undergoes a rapid translocation from the cytoplasm to the nucleus in response to apoptotic stimuli (4). Using a caspase-2 antibody specific to just the active form of caspase-2 offers the advantage of examining a subpopulation of caspase-2 separately from the global population. This tool will help elucidate the cellular processing mechanisms of caspase-2. Additionally, immunoprecipitation with caspase-2 antibodies may help identify caspase-2 substrates or effectors.
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