The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein

Ramesh Hegde, Srinivasa M. Srinivasula, Pinaki Datta, Muniswamy Madesh, Richard Wassell, Zhi Jia Zhang, Na Eun Cheong, Julie Nejmeh, Teresa Fernandes-Alnemri, Shin Ichi Hoshino, Emad S. Alnemri

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)38699-38706
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number40
DOIs
StatePublished - Oct 3 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Hegde, R., Srinivasula, S. M., Datta, P., Madesh, M., Wassell, R., Zhang, Z. J., Cheong, N. E., Nejmeh, J., Fernandes-Alnemri, T., Hoshino, S. I., & Alnemri, E. S. (2003). The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein. Journal of Biological Chemistry, 278(40), 38699-38706. https://doi.org/10.1074/jbc.M303179200