MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death

• Published in: Proceedings of the National Academy of Sciences - PNAS 1997-10, Vol.94 (21), p.11333-11338
• Main Authors: Han, D K, Chaudhary, P M, Wright, M E, Friedman, C, Trask, B J, Riedel, R T, Baskin, D G, Schwartz, S M, Hood, L
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Animals; Apoptosis; Arabidopsis Proteins; bcl-X Protein; Biological Sciences; Carrier Proteins - biosynthesis; Carrier Proteins - chemistry; Carrier Proteins - metabolism; CASP8 and FADD-Like Apoptosis Regulating Protein; Caspase 1; Cell Line; Cellular biology; Cricetinae; Cysteine Endopeptidases - chemistry; Cysteine Endopeptidases - metabolism; Fatty Acid Desaturases - chemistry; Fatty Acid Desaturases - metabolism; Female; Genes; Humans; Intracellular Signaling Peptides and Proteins; Lymphocytes - immunology; Lymphocytes - metabolism; Mammals; Molecular Sequence Data; Organ Specificity; Plant Proteins - chemistry; Plant Proteins - metabolism; Pregnancy; Proteins; Proto-Oncogene Proteins c-bcl-2 - chemistry; Proto-Oncogene Proteins c-bcl-2 - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Sequence Alignment; Sequence Deletion; Sequence Homology, Amino Acid; Transcription, Genetic; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.21.11333

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.