MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL 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 BclXL and FLICE in mammalian cells. Thus, MRIT is a mammalian protein that interacts simultaneously with both caspases and a Bcl-2 family member.
Han
D K
DK
Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Chaudhary
P M
PM
Wright
M E
ME
Friedman
C
C
Trask
B J
BJ
Riedel
R T
RT
Baskin
D G
DG
Schwartz
S M
SM
Hood
L
L
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D029681:Arabidopsis Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D020170:Caspase 1; D002460:Cell Line; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008322:Mammals; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection; D051020:bcl-X Protein
D029681:Arabidopsis Proteins; C494811:BCL2L1 protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010940:Plant Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051020:bcl-X Protein; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; D003546:Cysteine Endopeptidases; D020170:Caspase 1