title: Calpain mediates processing of the translation termination factor eRF3 into the IAP-binding isoform p-eRF3.
abstract: The involvement of polypeptide chain-releasing factor eRF3 in translation termination and mRNA decay is well established. Moreover, the finding that the proteolytically processed isoform of eRF3 (p-eRF3) interacts with inhibitors of apoptosis proteins (IAPs) to activate caspase, implies that eRF3 is a cell death regulator. However, the protease(s) responsible for p-eRF3 production and how p-eRF3 regulates apoptosis remain unknown. Here, we show that calpain mediates p-eRF3 production in vitro and in living cells. p-eRF3 is produced in cells treated with ER stressors in a calpain-dependent manner. These findings suggest that p-eRF3 is a novel regulator of calpain-dependent cell death.
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Inagaki
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan. Electronic address: hoshino@phar.nagoya-cu.ac.jp.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hoshino
mesh_terms: D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress; D057809:HEK293 Cells; D006801:Humans; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D059748:Proteolysis; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D010454:Peptide Termination Factors; D020033:Protein Isoforms; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C087971:peptide-chain-release factor 3; D002154:Calpain; D002118:Calcium
keywords: Apoptosis; Calpain; Inhibitor of apoptosis protein; Translation termination; eRF3