FUNCTIONAL ACTIVATION OF NEDD2 ICH-1 (CASPASE-2) IS AN EARLY PROCESS IN APOPTOSIS/

The ICE/CED-3 family of proteases (caspases) play a central role in th e execution phase of apoptosis, These proteases are synthesised as pre cursor molecules that require processing at specific aspartate residue s to pro duce the two subunits that comprise the active enzyme. The ac tivation of some of these proteases has been shown to occur during apo ptosis. Here we show that Nedd2/ICH-1 (caspase-2) is activated during apoptosis induced by a variety of apoptotic stimuli, This activation o ccurs very early upon treatment of cells with apoptotic agents and app ears to precede the activation of CPP32 (caspase-3). The activation of Nedd2 was not seen in cells that are resistant to apoptosis, These ob servations suggest that Nedd2 is an early effector in the pathway lead ing to cell death. Our observations also lend weight to the hypothesis that a group of caspases containing long prodomains are the first to be activated in response to apoptotic signals and that they lie upstre am of a second class of caspases such as CPP32 containing short or no prodomains.