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
- Boldin MP
- Goncharov TM
- Goltsev YV
- Wallach D
June 14, 1996
- Adaptor Proteins, Signal Transducing
- Amino Acid Sequence
- Antigens, CD
- Antigens, CD95
- Base Sequence
- Caenorhabditis elegans Proteins
- Carrier Proteins
- Caspase 1
- Cell Line
- Cloning, Molecular
- Cysteine Endopeptidases
- DNA-Binding Proteins
- Fas-Associated Death Domain Protein
- Helminth Proteins
- Molecular Sequence Data
- Organ Specificity
- Protein Binding
- 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
- Breast cancer, protection against is related to genes CASP8, MCH5, ALPS2B which are autosomal dominant according to the OMIM database.
- Immunodeficiency due to CASP8 deficiency is related to genes CASP8, MCH5, ALPS2B which are autosomal recessive according to the OMIM database.
- Lung cancer, protection against is related to genes CASP8, MCH5, ALPS2B which are autosomal recessive according to the OMIM database.
- Hepatocellular carcinoma, somatic is related to genes CASP8, MCH5, ALPS2B which are autosomal dominant; somatic mutation according to the OMIM database.