Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing*
-
Amino Acid Sequence
-
Antigens, CD / physiology*
-
Apoptosis / physiology*
-
Base Sequence
-
Caenorhabditis elegans Proteins
-
Carrier Proteins / metabolism*
-
Caspase 1
-
Caspases*
-
Cell Line
-
Cloning, Molecular
-
Cysteine Endopeptidases / genetics*
-
Cysteine Endopeptidases / metabolism
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Fas-Associated Death Domain Protein
-
Helminth Proteins / genetics
-
Humans
-
Kidney
-
Molecular Sequence Data
-
Organ Specificity
-
Protein Binding
-
Proteins / physiology
-
RNA, Messenger / analysis
-
Receptors, Tumor Necrosis Factor / physiology*
-
Receptors, Tumor Necrosis Factor, Type I
-
Recombinant Fusion Proteins / metabolism
-
Sequence Homology, Amino Acid
-
Signal Transduction / physiology
-
TNF Receptor-Associated Factor 1
-
fas Receptor / physiology*
Substances
-
Adaptor Proteins, Signal Transducing
-
Antigens, CD
-
Caenorhabditis elegans Proteins
-
Carrier Proteins
-
DNA-Binding Proteins
-
FADD protein, human
-
Fas-Associated Death Domain Protein
-
Helminth Proteins
-
Proteins
-
RNA, Messenger
-
Receptors, Tumor Necrosis Factor
-
Receptors, Tumor Necrosis Factor, Type I
-
Recombinant Fusion Proteins
-
TNF Receptor-Associated Factor 1
-
fas Receptor
-
Caspases
-
Cysteine Endopeptidases
-
ced-3 protein, C elegans
-
Caspase 1
Associated data
-
GENBANK/X98172
-
GENBANK/X98173
-
GENBANK/X98174
-
GENBANK/X98175
-
GENBANK/X98176
-
GENBANK/X98177
-
GENBANK/X98178