Caspase-mediated cleavage of eukaryotic translation initiation factor subunit 2α

Shinya Satoh, Makoto Hijikata, Hiroshi Handa, Kunitada Shimotohno

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Eukaryotic translation initiation factor 2α (eIF-2α), a target molecule of the interferon-inducible double-stranded-RNA-dependent protein kinase (PKR), was cleaved in apoptotic Saos-2 cells on treatment with poly(I)·poly(C) or tumour necrosis factor α. This cleavage occurred with a time course similar to that of poly(ADP-ribose) polymerase, a well-known caspase substrate. In addition, eIF-2α was cleaved by recombinant active caspase-3 in vitro. By site-directed mutagenesis, the cleavage site was mapped to an Ala-Glu-Val-Asp300↓Gly301 sequence located in the C-terminal portion of eIF-2α. PKR phosphorylates eIF-2α on Ser51, resulting in the suppression of protein synthesis. PKR-mediated translational suppression was repressed when the C-terminally cleaved product of eIF-2α was overexpressed in Saos-2 cells, even though PKR can phosphorylate this cleaved product. These results suggest that caspase-3 or related protease(s) can modulate the efficiency of protein synthesis by cleaving the α subunit of eIF-2, a key component in the initiation of translation.

Original languageEnglish
Pages (from-to)65-70
Number of pages6
JournalBiochemical Journal
Volume342
Issue number1
DOIs
Publication statusPublished - Aug 15 1999
Externally publishedYes

Keywords

  • Double-stranded-RNA-dependent protein kinase
  • Phosphorylation
  • Translational control

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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