Need for caspase-2 in apoptosis of growth-factor-deprived PC12 cells.

Previous studies have shown that caspases (proteases related to interleukin-1beta converting enzyme) are needed for the death of trophic factor-deprived PC12 cells. However, the protease involved in this process has not been identified. The results presented here strongly suggest that caspase-2 (Nedd2/Ich-1) plays a major role in the death of serum-deprived PC12 cells. We show that in PC12 cells overexpression of caspase-2 induces cell death, serum deprivation induces processing (i.e., activation) of the 48-kDa pro-caspase-2, and stable expression of caspase-2 antisense RNA inhibits apoptosis induced by serum deprivation. In addition, overexpression of bcl-2, which prevents this death process, also inhibits the processing of pro-caspase-2, suggesting that bcl-2 acts upstream of pro-caspase-2 activation.