title: MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death.
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.
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Han
authors.forename: P M
authors.initials: PM
authors.lastname: Chaudhary
authors.forename: M E
authors.initials: ME
authors.lastname: Wright
authors.forename: C
authors.initials: C
authors.lastname: Friedman
authors.forename: B J
authors.initials: BJ
authors.lastname: Trask
authors.forename: R T
authors.initials: RT
authors.lastname: Riedel
authors.forename: D G
authors.initials: DG
authors.lastname: Baskin
authors.forename: S M
authors.initials: SM
authors.lastname: Schwartz
authors.forename: L
authors.initials: L
authors.lastname: Hood
mesh_terms: 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
chemical_list: 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