Involvement of MACH, a Novel MORT1/FADD-interacting Protease, in Fas/APO-1- And TNF Receptor-Induced Cell Death

Cell. 1996 Jun 14;85(6):803-15. doi: 10.1016/s0092-8674(00)81265-9.

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