The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein.
Smac/Diablo and HtrA2/Omi are inhibitors of apoptosis (IAP)-binding proteins released from the mitochondria of human cells during apoptosis and regulate apoptosis by liberating caspases from IAP inhibition. Here we describe the identification of a proteolytically processed isoform of the polypeptide chain-releasing factor GSPT1/eRF3 protein, which functions in translation, as a ... new IAP-binding protein. In common with other IAP-binding proteins, the processed GSPT1 protein harbors a conserved N-terminal IAP-binding motif (AKPF). Additionally, processed GSPT1 interacts biochemically with IAPs and could promote caspase activation, IAP ubiquitination and apoptosis. The IAP-binding motif of the processed GSPT1 is absolutely required for these activities. Our findings are consistent with a model whereby processing of GSPT1 into the IAP-binding isoform could potentiate apoptosis by liberating caspases from IAP inhibition, or target IAPs and the processed GSPT1 for proteasome-mediated degradation.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Apoptosis, Blotting, Western, Caspases, Cell Line, Cloning, Molecular, Cysteine Endopeptidases, Cytochrome c Group, DNA, Complementary, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Endoplasmic Reticulum, Enzyme Activation, Epitopes, Glutathione Transferase, Humans, Microscopy, Confocal, Mitochondria, Molecular Sequence Data, Multienzyme Complexes, Peptide Termination Factors, Proteasome Endopeptidase Complex, Protein Binding, Protein Biosynthesis, Protein Isoforms, Protein Structure, Tertiary, Recombinant Proteins, Sequence Homology, Amino Acid, Subcellular Fractions, Time Factors, Transfection, Tumor Cells, Cultured, Ubiquitin
Amino Acid Motifs, Amino Acid Sequence, Apoptosis, Blotting, Western, Caspases, Cell Line, Cloning, Molecular, Cysteine Endopeptidases, Cytochrome c Group, DNA, Complementary, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Endoplasmic Reticulum, Enzyme Activation, Epitopes, Glutathione Transferase, Humans, Microscopy, Confocal, Mitochondria, Molecular Sequence Data, Multienzyme Complexes, Peptide Termination Factors, Proteasome Endopeptidase Complex, Protein Binding, Protein Biosynthesis, Protein Isoforms, Protein Structure, Tertiary, Recombinant Proteins, Sequence Homology, Amino Acid, Subcellular Fractions, Time Factors, Transfection, Tumor Cells, Cultured, Ubiquitin
J. Biol. Chem.
Date: Oct. 03, 2003
PubMed ID: 12865429
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