A PREEXISTING PROTEASE IS A COMMON EFFECTOR OF THYMOCYTE APOPTOSIS MEDIATED BY DIVERSE STIMULI

Data from a number of model systems support a role for proteolysis in apoptotic cell death. Using immature rat thymocytes, we demonstrate th at the inhibitors N-tosyl-L-Iysyl chloromethylketone (TLCK) and N-tosy l-L-phenylalanyl chloromethylketone (TPCK) have very different effects on apoptosis. TLCK inhibits apoptosis induced by diverse stimuli at a n early stage prior to both DNA fragmentation and cytoplasmic changes. We show that the TLCK-sensitive target is pre-existing and not synthe sized in response to apoptotic stimuli. The contrasting effects of TLC K and TPCK support the hypothesis that the TLCK target is a trypsin-li ke protease which is a common effector of thymocyte apoptosis.