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.
Pubmed ID: 8681376 RIS Download
Adaptor Proteins, Signal Transducing | Amino Acid Sequence | Antigens, CD | Antigens, CD95 | Apoptosis | Base Sequence | Caenorhabditis elegans Proteins | Carrier Proteins | Caspase 1 | Caspases | Cell Line | Cloning, Molecular | Cysteine Endopeptidases | DNA-Binding Proteins | Fas-Associated Death Domain Protein | Helminth Proteins | Humans | Kidney | Molecular Sequence Data | Organ Specificity | Protein Binding | Proteins | RNA, Messenger | Receptors, Tumor Necrosis Factor | Receptors, Tumor Necrosis Factor, Type I | Recombinant Fusion Proteins | Sequence Homology, Amino Acid | Signal Transduction | TNF Receptor-Associated Factor 1