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 language | English (US) |
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Pages (from-to) | 255-265 |
Number of pages | 11 |
Journal | Molecular and Cellular Biochemistry |
Volume | 403 |
Issue number | 1-2 |
DOIs | |
State | Published - May 1 2015 |
Externally published | Yes |
Keywords
- Abrin
- Active site
- Apoptosis
- Inhibition of protein synthesis
ASJC Scopus subject areas
- Molecular Biology
- Clinical Biochemistry
- Cell Biology