Inhibition of protein synthesis leading to unfolded protein response is the major event in abrin-mediated apoptosis

Ritu Mishra, Meenakshi Sundaram Kumar, Anjali A. Karande

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Abrin obtained from the plant Abrus precatorius inhibits protein synthesis and also triggers apoptosis in cells. Previous studies from our laboratory suggested a link between these two events. Using an active site mutant of abrin A-chain which exhibits 225-fold lower protein synthesis inhibitory activity than the wild-type abrin A-chain, we demonstrate in this study that inhibition of protein synthesis induced by abrin is the major factor triggering unfolded protein response leading to apoptosis. Since abrin A-chain requires the B-chain for internalization into cells, the wild-type and mutant recombinant abrin A-chains were conjugated to native ricin B-chain to generate hybrid toxins, and the toxic effects of the two conjugates were compared. The rate of inhibition of protein synthesis mediated by the mutant ricin B-rABRA (R167L) conjugate was slower than that of the wild-type ricin B-rABRA conjugate as expected. The mutant conjugate activated p38MAPK and caspase-3 similar to its wild-type counterpart although at later time points. Overall, these results confirm that inhibition of protein synthesis is the major event contributing to abrin-mediated apoptosis.

Original languageEnglish (US)
Pages (from-to)255-265
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume403
Issue number1-2
DOIs
StatePublished - May 1 2015
Externally publishedYes

Keywords

  • Abrin
  • Active site
  • Apoptosis
  • Inhibition of protein synthesis

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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