MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclX(L) and initiates cell death

Activation of the cascade of proteolytic caspases has been identified as the final common pathway of apoptosis in diverse biological systems. We have isolated a gene, termed MRIT, that possesses overall sequence homology to FLICE (MACH), a large prodomain caspase that links the aggregated complex of the death domain receptors of the tumor necrosis factor receptor family to downstream caspases, However, unlike FLICE, the C-terminal domain of MRIT lacks the caspase catalytic consensus sequence QAC(R/Q)G. Nonetheless MRIT activates caspase dependent death, Using yeast two-hybrid assays, we demonstrate that MRIT associates with caspases possessing large and small prodomains (FLICE, and CPP32/YAMA), as well as with the adaptor molecule FADD, In addition, MRIT simultaneously and independently interacts with BclX(L) and FLICE in mammalian cells, Thus, MRIT is a mammalian protein that interacts simultaneously with both caspases and a Bcl-2 family member.