Commitment to cell death is signaled by the appearance of a terminin protein of 30 kDa.

Programmed cell death appears to be regulated by a specific molecular program, often dependent upon the activation of unique genes. We have identified terminin in the 60-kDa form as the unique subspecies present only in senescent human diploid fibroblasts. In this report, the biochemical properties of terminin during the process of induced cell death in Swiss 3T3 cells is investigated by total removal of serum, which subsequently activates apoptosis as determined by DNA degradation. Evidence presented here indicates that a specific proteolytic cleavage of terminin proteins occurs during apoptosis, leading to the appearance of a protein species with a molecular mass of 30 kDa (Tp-30) in serum-deprived mouse 3T3 cells. The appearance of Tp-30 can be modulated up to 24 h after serum deprivation by pretreatment with cycloheximide or returning to serum-containing conditions. These studies thus define the association of apoptosis-specific proteolysis of terminin and the appearance of Tp-30 with cell death in mouse 3T3 fibroblasts and can serve as a marker for cells on their way to apoptosis.