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Ribosome-Inactivating Proteins: From Plant Defense to Tumor Attack

Author(s): Maddalena de Virgilio | Alessio Lombardi | Rocco Caliandro | Maria Serena Fabbrini

Journal: Toxins ISSN 2072-6651
Volume: 2; Issue: 11; Start page: 2699; Date: 2010;
Original page

Keywords: ribosome-inactivating proteins | cancer immunotherapy | ITs | vascular leak syndrome | recombinant expression | fusion toxins | single chain antibody variable fragments | Pichia pastoris

ABSTRACT
Ribosome-inactivating proteins (RIPs) are EC3.2.32.22 N-glycosidases that recognize a universally conserved stem-loop structure in 23S/25S/28S rRNA, depurinating a single adenine (A4324 in rat) and irreversibly blocking protein translation, leading finally to cell death of intoxicated mammalian cells. Ricin, the plant RIP prototype that comprises a catalytic A subunit linked to a galactose-binding lectin B subunit to allow cell surface binding and toxin entry in most mammalian cells, shows a potency in the picomolar range. The most promising way to exploit plant RIPs as weapons against cancer cells is either by designing molecules in which the toxic domains are linked to selective tumor targeting domains or directly delivered as suicide genes for cancer gene therapy. Here, we will provide a comprehensive picture of plant RIPs and discuss successful designs and features of chimeric molecules having therapeutic potential.