Note: Intro -- Toxic Plant Proteins -- Editors -- Preface -- Contents -- Evolution of Plant Ribosome-Inactivating Proteins -- 1 Introduction -- 2 General Overview of the Taxonomic Distribution of A and B Domains within the Viridiplantae -- 3 Overview of the Taxonomic Distribution of A and B Domains within the Magnoliophyta (Flowering Plants) -- 3.1 ``Classical´´ Type 2 RIPs (AB proteins) -- 3.2 Other Proteins with Ricin- Domains -- 4 Molecular Evolution of Type 2 RIPs -- 4.1 General Observations Concerning the Taxonomic Distribution of Type 2 RIPs and the Occurrence of Multiple Paralogs -- 4.2 Overall Phylogeny of Type 2 RIPs -- 4.3 Special Evolutionary Events: Gene Amplification and Generation of Type A and Type B Proteins from Genuine Type 2 RIPs -- 4.4 What is the Origin of Type 2 RIP Genes? -- 4.4.1 Origin of the B-hain -- 4.4.2 Origin of the A-hain -- 5 Molecular Evolution of Type 1 RIPs -- 5.1 Dicots and Monocots Other Than Poaceae -- 5.2 Poaceae Type 1 RIPs -- 5.2.1 O. sativa -- 5.2.2 Andropogoneae: Z. mays and Sorghum bicolor -- 5.2.3 Pooideae -- 5.2.4 Relationships between the RIPs from Poaceae and Other Seed Plants -- 6 What is the Relationship between Plant and Bacterial RIPs? -- 7 Chimeric RIPs Other Than Type 2 RIPs -- 7.1 JIP60 and Other Type AC Chimeric RIPs -- 7.2 Chimeric RIP with a C-erminal D Domain -- 8 Conclusions -- References -- RNA N-Glycosidase Activity of Ribosome-Inactivating Proteins -- 1 Introduction -- 2 Ricin as an RNA N-lycosidase -- 2.1 28S rRNA as the Target of Modification by Ricin and Other RIPs -- 2.2 RNA N-lycosidase Activity of Ricin A-hain -- 2.3 Other RIPs -- 2.4 Major Role of RNA in Protein Synthesis -- 3 Ribosomal Mechanisms Involving the Sarcin-icin Domain -- 3.1 Eukaryotic Translation Can Be Inhibited Strongly by Dysfunction of a Small Fraction of the Ribosome Population. , 3.2 Difference in the Modes of Action between α-arcin and Ricin -- 3.3 Substrate Specificity -- 3.4 Structure of the SRL -- 4 Ribosomal RNA Apurinic Site-pecific Lyase: Intrinsic Stability of the Ribosome -- References -- Enzymatic Activities of Ribosome-Inactivating Proteins -- 1 Introduction -- 2 Action of RIPs on Ribosomes and rRNA -- 2.1 Site of Modification by RIPs -- 2.2 Structural Requirements in Ribosomal RNA for RIP Action -- 3 Polynucleotide:Adenosine Glycosidase Activity -- 3.1 5 Cap-ndependent Activity -- 3.2 5 Cap-ependent Activity -- 4 DNA Lyase -- 5 Bifunctional Enzymes with RIP Activity in Which the Non-IP Activity Acts on Non-ucleic Acid Substrates -- 5.1 Lipase -- 5.2 Chitinase -- 5.3 Superoxide Dismutase -- 6 Conclusions -- References -- Type I Ribosome-Inactivating Proteins from Saponaria officinalis -- 1 Introduction -- 2 Saporin Multigene Family and Saporin Isoforms -- 3 Saporin Biochemical Features -- 3.1 Saporin Structure -- 3.2 Saporin Catalytic Activity -- 3.3 Residues Important for the Catalytic Activity -- 3.4 Interaction with the Ribosome -- 3.5 Saporin Inhibitors -- 4 Saporin Trafficking and Toxicity in Eukaryotic Cells -- 4.1 Subcellular Distribution of Saporin Isoforms in Soapwort Tissues -- 4.2 Saporin Biosynthesis and Role in Planta -- 4.3 Intoxication Pathways in Mammalian Cells -- 5 Heterologous Expression of Saporin and Saporin Fusion Toxins -- 6 Conclusions and Perspectives -- References -- Type 1 Ribosome-Inactivating Proteins from the Ombú Tree (Phytolacca dioica L.) -- 1 Introduction -- 2 RIPs from P. dioica L. -- 2.1 Isolation of RIPs from Seeds and Leaves of P. dioica -- 2.2 Basic Characteristics of RIPs from Seeds and Leaves of P. dioica -- 2.3 Differential Seasonal and Age Expression in Leaves -- 2.4 Cellular Localization -- 2.5 Glycosylation of P. dioica RIPs -- 3 Enzymatic and Biological Characteristics. , 3.1 Neta-lycosidase and APG Activities -- 3.2 Toxicity to Mice -- 3.3 Immunotoxin -- 3.4 Cross-eactivity -- 3.5 Activity on Double-tranded pBR322 DNA -- 4 X-ay Crystal Structure of P. dioica RIPs -- 4.1 Atomic Resolution Studies of PD-4: A Reference RIP Structure -- 4.2 An Insight into the Active Site of PD-4: Tyr72 as a Substrate Carrier Through pi- Stacking Interactions with Aden -- 4.3 PD-1 and PD-4 -Two Homologous Proteins with Distinct Functional Properties -- 5 Concluding Remarks -- References -- Sambucus Ribosome-Inactivating Proteins and Lectins -- 1 Ribosome-nactivating Proteins -- 2 Occurrence and Structural Diversity of Sambucus Proteins -- 3 Similarity and Processing -- 4 Structure -- 5 Enzymic Activity -- 6 Toxicity to Cells and Animals -- 7 Interaction with Cells -- 8 Phylogenetic Relationship Among the RIPs and Lectins from Sambucus -- 9 Uses of the RIPs and Lectins From Sambucus -- References -- Ribosome-Inactivating Proteins from Abrus pulchellus -- 1 Introduction -- 2 Pulchellin Isoforms -- 3 The Heterologous Expression of Pulchellins -- 3.1 The Pulchellin A-hain -- 3.2 The Pulchellin B-hain -- 4 Pulchellin Endocytosis in Mammalian Cells -- 5 Structure of Pulchellin -- 6 Conclusion -- References -- Ribosome-Inactivating Proteins in Cereals -- 1 Introduction -- 2 Classification of RIPs -- 3 Applied Research on RIPs -- 4 Properties of Cereal RIPs -- 4.1 Rice RIPs -- 4.2 Wheat RIPs -- 4.3 Barley RIPs -- 4.4 Maize RIPs -- 5 Transgenic Plants Expressing RIPs -- 6 Conclusions -- References -- Ribosome Inactivating Proteins and Apoptosis -- 1 Introduction -- 2 Mechanism of Action of RIPs -- 3 Apoptosis -- 4 Ribosome Inactivating Proteins and Apoptosis -- 4.1 Activation of Intrinsic Pathway of Apoptosis by General Stress -- 4.2 Activation of the Extrinsic Pathway of Apoptosis -- 4.3 Impaired Balance Between and Pro-and Anti-poptotic Factors. , 4.4 Induction of Apoptosis in Response to Ribotoxic Stress -- 4.5 The Intrinsic Nuclease Activity of Toxins -- 4.6 Alternate Pathways -- 4.6.1 PARP Activation Resulting in NAD+Depletion -- 4.6.2 Down-egulation of Telomerase -- 4.6.3 Inhibition of Histone Deacetylase -- 4.6.4 Degradation of Cytoskeleton Proteins -- 4.6.5 Nitric Oxide-ediated Apoptosis Pathway -- 5 Conclusion -- References -- The Synthesis of Ricinus communis Lectins -- 1 Introduction -- 2 Ricin -- 2.1 Synthesis and Quality Control of Proricin -- 2.1.1 Synthesis and ER Translocation -- 2.1.2 Anterograde Trafficking -- 2.2 Ricin A Chain: ER Synthesis and Turnover in the Cytosol -- 2.3 Ricin B Chain: Synthesis and Quality Control -- 3 RCA 1 -- 3.1 RCA Synthesis and Assembly -- 4 Concluding Remarks -- References -- How Ricin Reaches its Target in the Cytosol of Mammalian Cells -- 1 Introduction -- 2 Cytotoxicity Model -- 3 Cell Entry -- 3.1 Cell Surface Events Remain Cryptic -- 3.2 Retrograde Trafficking -- 3.3 Ricin Is Delivered to the ER -- 3.4 Ricin Is Reduced to its Constituent Chains in the ER -- 3.5 RTA Unfolds in the ER -- 3.6 Chaperone Interactions in the ER -- 3.7 The Dislocation Process for RTA Remains Mysterious -- 4 Recovery of Activity in the Cytosol -- 5 Conclusions -- References -- Ribosome-Inactivating Protein-Containing Conjugates for Therapeutic Use -- 1 Introduction -- 2 Distribution -- 2.1 Enzymatic Activity -- 2.2 Toxicity -- 3 Properties of RIPs -- 3.1 Other Biological Properties -- 3.2 Possible Uses -- 3.3 Role in Nature -- 4 RIP-Based Immunotoxins -- 4.1 Chemical Immunotoxins -- 4.2 Recombinant Immunotoxins -- 4.3 In Vitro Cytotoxicity -- 4.4 Enhancement of Cytotoxicity -- 4.4.1 Lysosomotropic Amines and Carboxylic Ionophores -- 4.4.2 Ammonium Chloride (NH4Cl) -- 4.4.3 Chloroquine -- 4.4.4 Other Lysosomotropic Amines (Methylamine, Amantadine). , 4.4.5 Carboxylic Ionophores -- 4.4.6 Antagonists of Ca++ Channels and Other Compounds3.4.6 Antagonists of Ca++ channels and other compounds -- 4.4.7 Verapamil and Its Derivatives -- 4.4.8 Perhexiline and Indolizines -- 4.4.9 Ricin B-Chain -- 4.4.10 Viruses -- 4.4.11 Saponins -- 5 Animal Studies -- 6 Ex Vivo Bone Marrow Purging with Immunotoxins -- 7 Clinical Studies -- 7.1 Hematologic Tumors -- 7.1.1 Hodgkin´s Lymphoma -- 7.1.2 Non-Hodgkin´s Lymphoma -- 7.1.3 Leukemia -- 7.1.4 Multiple Myeloma -- 7.1.5 Cutaneous Lymphoma -- 7.2 Cerebrospinal Fluid Spread of Tumors -- 7.3 Solid Tumors -- 7.3.1 Small-Cell Lung Cancer (SCLC) -- 7.3.2 Bladder Cancer -- 7.3.3 Breast Tumors -- 7.3.4 Colon Carcinoma -- 7.3.5 Melanoma -- 8 Autoimmune Diseases -- 8.1 RA -- 8.2 SLE -- 9 Other Applications -- 9.1 Corneal Opacification -- 10 Problems and Opportunities in the Future Development of Immunotoxins -- 10.1 Selection of Patients -- 10.2 Immunogenicity -- 10.3 Side Effects -- 11 Conclusions -- References -- Index.