Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.
Fas/APO-1 and p55 tumor necrosis factor (TNF) receptor (p55-R) activate cellular mechanisms that result in cell death. Upon activation of these receptors, Fas/APO-1 binds a protein called MORT1 (or FADD) and p55-R binds a protein called TRADD. MORT1 and TRADD can also bind to each other. We have cloned a novel protein, MACH, that binds to MORT1. This protein exists in multiple isoforms, some of which contain a region that has proteolytic activity and shows marked sequence homology to proteases of the ICE/CED-3 family. Cellular expression of the proteolytic MACH isoforms results in cell death. Expression of MACH isoforms that contain an incomplete ICE/CED-3 region provides effective protection against the cytotoxicity induced by Fas/APO-1 or p55-R triggering. These findings suggest that MACH is the most upstream enzymatic component in the Fas/APO-1- and p55-R-induced cell death signaling cascades.
Boldin
M P
MP
Department of Membrane Research and Biophysics, The Weizmann Institute of Science, Rehovot, Israel.
Goncharov
T M
TM
Goltsev
Y V
YV
Wallach
D
D
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1; D020169:Caspases; D002460:Cell Line; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein; D015801:Helminth Proteins / Q000235:genetics; D006801:Humans; D007668:Kidney; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011485:Protein Binding; D011506:Proteins / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D047990:TNF Receptor-Associated Factor 1; D019014:fas Receptor / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D015801:Helminth Proteins; D011506:Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins; D047990:TNF Receptor-Associated Factor 1; D019014:fas Receptor; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans; D020170:Caspase 1