Cytotoxic Mechanisms of Ribosome-Inactivating Proteins and Related Immunotoxins

Dear Colleagues,

Ribosome-inactivating proteins (RIPs) are toxic plant enzymes with rRNA N-glycosylase activity that can remove a specific adenine residue from 28S rRNA, thus causing the irreversible inhibition of protein synthesis and cell death. In addition, some authors have reported that RIPs are able to deadenylate several other substrates such as poly(A), mRNA, tRNA, and DNA, thus displaying polynucleotide:adenine glycosylase activity.

For many years, rRNA deadenylation was thought to be the only enzymatic activity of RIPs, and ribosome inactivation was considered the pivotal event in cell death triggering. Apoptotic changes in cells intoxicated with ricin or abrin were firstly described in 1987, and subsequently, apoptosis was commonly considered the typical mode of RIP-induced cell death. However, several lines of experimental evidence demonstrate that RIP intoxication can induce multiple cell death pathways, involving at least apoptosis, necroptosis and autophagy. Moreover, it is now evident that RIPs can induce apoptosis regardless of protein synthesis inhibition. Despite the progress made in the knowledge of the pathogenetic mechanisms of these molecules, many points still need to be clarified. Among these are the primary molecular events induced by RIP intoxication, the correlation between the cell differentiation degree and RIP sensitivity, the interconnection between different cell death pathways, and the timing of all these events.

RIPs have been used in many experimental strategies in medicine, in order to specifically destroy cells responsible for pathological conditions. These plant toxins have been tested as native molecules, in locoregional treatments, or as toxic components of immunotoxins for experimental therapy in several pathologies, ranging from cancer and pain control to autoimmune diseases and transplant rejection. The elucidation of the molecular details of cell intoxication by RIP is a fundamental requirement for building increasingly effective immunotoxins and predicting, in part, their possible side effects.

The aim of this Special Issue is to collect original articles, reviews and short communications that provide readers with a comprehensive and clear overview of the cell stress mechanisms and death pathways induced by RIPs.

Dr. Andrea Bolognesi
Guest Editor

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