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Caspase-2 is not required for thymocyte or neuronal apoptosis even though cleavage of caspase-2 is dependent on both Apaf-1 and caspase-9
Authors:O'Reilly L A  Ekert P  Harvey N  Marsden V  Cullen L  Vaux D L  Hacker G  Magnusson C  Pakusch M  Cecconi F  Kuida K  Strasser A  Huang D C S  Kumar S
Institution:The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia. oreilly@wehi.edu.au
Abstract:We have generated rat monoclonal antibodies that specifically recognise caspase-2 from many species, including mouse, rat and humans. Using these antibodies, we have investigated caspase-2 expression, subcellular localisation and processing. We demonstrate that caspase-2 is expressed in most tissues and cell types. Cell fractionation and immunohistochemistry experiments show that caspase-2 is found in the nuclear and cytosolic fractions, including a significant portion present in the Golgi complex. We found that caspase-2 is processed in response to many apoptotic stimuli but experiments with caspase-2 deficient mice demonstrated that it is not required for apoptosis of thymocytes or dorsal root ganglia (DRG) neurons in response to a variety of cytotoxic stimuli. Caspase-2 processing does not occur in thymocytes lacking Apaf-1 or caspase-9, suggesting that in this cell type, activation of caspase-2 occurs downstream of apoptosome formation.
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