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Ribosome-inactivating proteins (RIPs), mostly from plants, are enzymes which depurinate rRNA, thus inhibiting protein synthesis. They also depurinate other polynucleotide substrates. The biological activity of RIPs is not completely clarified, and sometimes independent of the inhibition of protein synthesis. There are differences in the cytotoxicity of RIPs and, consequently, in their toxicity to animals. Some RIPs are potent toxins, the best known being ricin, a potential biological weapon. New toxins have recently been identified. RIPs cause apoptotic and necrotic lesions, and induce production of cytokines causing inflammation. RIPs are potentially useful in agriculture and medicine because (i) they have antiviral activity and (ii) they are used for the preparation of conjugates with antibodies ('immunotoxins') or other carriers, rendering them specifically toxic to the cell target of the carrier, which may be helpful in therapy. The distribution, mechanism of action and role in nature of RIPs are not completely understood, and we can expect several future developments in their practical application.

Plant ribosome-inactivating proteins (RIPs) are N-glycosidases which cleave the N-glycosidic bond of adenine in a specific ribosomal RNA sequence. Most commonly RIPs are single-chain proteins (type 1 RIPs), but some (type 2 RIPs) possess a galactose-specific lectin domain that binds to cell surfaces. The latter RIPs are potent toxins, the best known of which is ricin. RIPs have antiviral and abortifacient activities, and, in a widespread application, can also be linked to antibodies or ligands to form immunotoxins or conjugates specifically toxic to a given type of cell.

Ribosome-inactivating proteins (RIP) are a family of plant enzymes for which a unique activity was determined: rRNAN-glycosidase at a specific universally conserved position, A4324in the case of rat ribosomes. Recently we have shown that the RIP from Saponaria officinalis have a much wider substrate specificity: they are actually polynucleotide:adenosine glycosidases. Here we extend studies on substrate specificity to most known RIP: 52 purified proteins, both type 1 (single-chain) and type 2 (two chain, an enzymatic chain and a lectin chain) were examined for adenine release on various substrates including RNAs from different sources, DNA, and poly(A). All RIP depurinated extensively DNA and some released adenine from all adenine-containing polynucleotides tested. From experimental evidence the entire class of plant proteins, up to now called ribosome-inactivating proteins, may be classified as polynucleotide:adenosine glycosidases. The newly identified substrates may be implicated in the biological role(s) of RIP.

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Ribosome-Inactivating Proteins (RIPs) are enzymes that trigger the catalytic inactivation of ribosomes and other substrates. They are present in a large number of plants and have been found also in fungi, algae and bacteria. RIPs are currently classified as type 1, those formed by a single polypeptide chain with the enzymatic activity, and type 2, those formed by 2 types of chains, i.e. A chains equivalent to a type 1 RIPs and B chains with lectin activity. Type 2 RIPs usually contain the formulae A-B, (A-B)2 and less frequent (A-B)4 and polymeric forms of type 2 RIPs lectins. RIPs are broadly distributed in plants, and are present also in fungi, bacteria, at least in one alga; recently RIP-type activity has been described in mammalian tissues. The highest number of RIPs has been found in Caryophyllaceae, Sambucaceae, Cucurbitaceae, Euphorbiaceae, Phytolaccaceae and Poaceae. However there are no systematic screening studies to allow generalisations about occurrence. The most known activity of RIPs is the translational inhibitory activity, which seems a consequence of a N-glycosidase on the 28 S rRNA of the eukaryotic ribosome that triggers the split of the A(4324) (or an equivalent base in other ribosomes), which is key for translation. This activity seems to be part of a general adenine polynucleotide glycosylase able to act on several substrates other than ribosomes, such as tRNA, mRNA, viral RNA and DNA. Other enzymatic activities found in RIPs are lipase, chitinase and superoxide dismutase. RIPs are phylogenetically related. In general RIPs from close families share good amino acid homologies. Type 1 RIPs and the A chains of type 2 RIPs from Magnoliopsida (dicotyledons) are closely related. RIPs from Liliopsida (monocotyledons) are at the same time closely related and distant from Magnoliopsida. Concerning the biological roles played by RIPs there are several hypotheses, but the current belief is that they could play significant roles in the antipathogenic (viruses and fungi), stress and senescence responses. In addition, roles as antifeedant and storage proteins have been also proposed. Future research will approach the potential biological roles played by RIPs and their use as toxic effectors in the construction of immunotoxins and conjugates for target therapy.

Ribosome-inactivating proteins (RIPS) from plants inactivate eukaryotic ribosomes, as far as studied by rendering their 60 S subunit unable to bind elongation factor 2. These proteins seem widely distributed and possibly ubiquitous in plants. They are either type 1, those consisting of a single polypeptide chain, or type 2 (ricin and related toxins), those consisting of two chains, one of which is a galactose-binding lectin. The literature on RIPS from 1982 has been reviewed with respect to (i) the chemical and biological properties of RIPS, (ii) their use for the preparation of immunotoxins and (iii) new perspectives. Ribosome-inactivating protein