Abstract
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 BclXL and FLICE in mammalian cells. Thus, MRIT is a mammalian protein that interacts simultaneously with both caspases and a Bcl-2 family member.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Amino Acid Sequence
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Animals
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Apoptosis*
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Arabidopsis Proteins*
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CASP8 and FADD-Like Apoptosis Regulating Protein
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Carrier Proteins / biosynthesis
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism*
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Caspase 1
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Cell Line
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Cricetinae
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Cysteine Endopeptidases / chemistry*
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Cysteine Endopeptidases / metabolism*
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Fatty Acid Desaturases / chemistry
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Fatty Acid Desaturases / metabolism
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Female
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Humans
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Intracellular Signaling Peptides and Proteins*
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Lymphocytes / immunology
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Lymphocytes / metabolism
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Mammals
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Molecular Sequence Data
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Organ Specificity
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Plant Proteins / chemistry
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Plant Proteins / metabolism
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Pregnancy
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Proto-Oncogene Proteins c-bcl-2 / chemistry
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Alignment
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Sequence Deletion
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Sequence Homology, Amino Acid
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Transcription, Genetic
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Transfection
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bcl-X Protein
Substances
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Arabidopsis Proteins
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BCL2L1 protein, human
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CASP8 and FADD-Like Apoptosis Regulating Protein
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CFLAR protein, human
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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Plant Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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bcl-X Protein
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Fatty Acid Desaturases
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Fad7 protein, Arabidopsis
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Cysteine Endopeptidases
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Caspase 1