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

Mishra, Ritu and Kumar, Meenakshi Sundaram and Karande, Anjali A (2015) Inhibition of protein synthesis leading to unfolded protein response is the major event in abrin-mediated apoptosis. In: MOLECULAR AND CELLULAR BIOCHEMISTRY, 403 (1-2). pp. 255-265.

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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.

Item Type:	Journal Article
Publication:	MOLECULAR AND CELLULAR BIOCHEMISTRY
Publisher:	SPRINGER
Additional Information:	Copy right for this article belongs to the SPRINGER, VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
Keywords:	Abrin; Inhibition of protein synthesis; Active site; Apoptosis
Department/Centre:	Division of Biological Sciences > Biochemistry UG Programme
Date Deposited:	19 Jul 2015 09:21
Last Modified:	19 Jul 2015 09:21
URI:	http://eprints.iisc.ac.in/id/eprint/51828

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