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 sequenc e homology to FLICE (MACH), a large prodomain caspase that links the a ggregated 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 se quence QAC(R/Q)G. Nonetheless MRIT activates caspase dependent death, Using yeast two-hybrid assays, we demonstrate that MRIT associates wit h caspases possessing large and small prodomains (FLICE, and CPP32/YAM A), as well as with the adaptor molecule FADD, In addition, MRIT simul taneously and independently interacts with BclX(L) and FLICE in mammal ian cells, Thus, MRIT is a mammalian protein that interacts simultaneo usly with both caspases and a Bcl-2 family member.