caa a22 4500 606236740 CHVBK 20210128101249.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s11010-015-2355-9 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2355-9 Inhibition of protein synthesis leading to unfolded protein response is the major event in abrin-mediated apoptosis [Elektronische Daten] [Ritu Mishra, Meenakshi Kumar, Anjali Karande] 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. Springer Science+Business Media New York, 2015 Abrin nationallicence Inhibition of protein synthesis nationallicence Active site nationallicence Apoptosis nationallicence Mishra Ritu Department of Biochemistry, Indian Institute of Science, 560012, Bangalore, Karnataka, India aut Kumar Meenakshi Undergraduate Studies, Indian Institute of Science, 560012, Bangalore, Karnataka, India aut Karande Anjali Department of Biochemistry, Indian Institute of Science, 560012, Bangalore, Karnataka, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 255-265 0300-8177 403:1-2<255 2015 403 11010 https://doi.org/10.1007/s11010-015-2355-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2355-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mishra Ritu Department of Biochemistry, Indian Institute of Science, 560012, Bangalore, Karnataka, India aut NATIONALLICENCE 700 1- Kumar Meenakshi Undergraduate Studies, Indian Institute of Science, 560012, Bangalore, Karnataka, India aut NATIONALLICENCE 700 1- Karande Anjali Department of Biochemistry, Indian Institute of Science, 560012, Bangalore, Karnataka, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 255-265 0300-8177 403:1-2<255 2015 403 11010