Ribosome-Inactivating Proteins From Plant Defense to Tumor Attack 英文参考文献.docVIP

Toxins 2010, 2, 2699-2737; doi:10.3390/toxins2112699 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Ribosome-Inactivating Proteins: From Plant Defense to Tumor Attack Maddalena de Virgilio 1, Alessio Lombardi 2, Rocco Caliandro 3 and Maria Serena Fabbrini 2,* 1 Istituto di Genetica Vegetale, Consiglio Nazionale delle Ricerche, Bari, Italy; E-Mail: maddalena.devirgilio@r.it 2 Istituto di Biologia e Biotecnologia Agraria, Consiglio Nazionale delle Ricerche, Milan, Italy; E-Mail: a.lombardi@r.it 3 Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Bari, Italy; E-Mail: rocco.caliandro@r.it * Author to whom correspondence should be addressed; E-Mail: fabbrini@r.it. Received: 20 October 2010; in revised form: 29 October 2010 / Accepted: 4 November 2010 / Published: 10 November 2010 Abstract: Ribosome-inactivating proteins (RIPs) are EC2 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. Keywords: ribosome-inactivating proteins; cancer immunotherapy; ITs; vascular leak syndrome; recombinant expression; fusion toxins; single chain antibody variable fragments; Pichia pastoris  Toxi