Ribosome inactivating protein saporin induces apoptosis through mitochondrial cascade, independent of translation inhibition.
Ribosome inactivating proteins (RIPs) are toxic translation inhibitors that kill eukaryotic cells by arresting protein synthesis at the translocation step. Saporin-6, expressed in the seeds of Saponaria officinalis plant, is a type I RIP comprising of a single polypeptide chain. Saporin is a specific RNA N-glycosidase and it removes a specific adenine residue from a conserved loop of the large rRNA of eukaryotic cells. Saporin-6 is one of the most potent of several isoforms of saporin, obtained from different tissues of the Saponaria plant. In addition to potently inhibiting translation, saporin has been also shown to induce cell death by apoptosis in different cellular models. To elucidate the mechanism of apoptosis induction by saporin, we have investigated the apoptotic pathway triggered by saporin. We have also analyzed whether the inhibition of protein synthesis by the toxin is the trigger for induction of apoptosis. We demonstrate that saporin-6 induces caspase-dependent apoptosis in U937 cells via the mitochondrial or intrinsic pathway. Unlike many other toxins the catalytic N-glycosidase activity of saporin is not required for apoptosis induction, and the apoptosis onset occurs before any significant inhibition of protein synthesis ensues.
Sikriwal
Deepa
D
Immunochemistry Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Ghosh
Paroma
P
Batra
Janendra K
JK
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D010940:Plant Proteins / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000378:metabolism / Q000633:toxicity*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D012276:Ricin / Q000378:metabolism / Q000494:pharmacology; D029750:Saponaria / Q000378:metabolism; D000076985:Saporins; D020298:U937 Cells; D019014:fas Receptor / Q000378:metabolism
D017304:Annexin A5; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D019014:fas Receptor; D045304:Cytochromes c; D012276:Ricin; D000076985:Saporins; D053148:Caspase 3; D053453:Caspase 9