Among plant toxins the most known are ribosome-inactivating proteins (RIPs), a family of enzymes widely spread in the plant kingdom, especially in angiosperms, but also present in some fungal and bacterial species.
RIPs are mainly classified as type 1, consisting of a single-chain protein with enzymatic activity, or type 2, consisting of an enzymatic A-chain linked by a disulfide bond to a lectin B-chain. The presence of the B-chain in type 2 RIPs makes them highly toxic for cells.
RIP activity was first identified as rRNA N-glycosylase (EC 3.2.2.22). RIPs specifically remove one adenine residue inside a GAGA sequence universally conserved among eukaryotic rRNA. Adenine removal damages ribosomes in an irreversible manner, causing inhibition of protein synthesis. RIPs are also able to deadenylate other substrates, such as DNA, mRNA, tRNA, and poly(A). For this reason, the enzymatic activity definition of these proteins has been proposed to be changed to polynucleotide: adenosine glycosylase.
RIPs have received much attention concerning their application in medicine. After linking to appropriate carriers, such as monoclonal antibodies (immunotoxins), these proteins have been used in experimental therapies to eliminate unwanted cells, responsible of pathological conditions, demonstrating particular efficacy against hematological malignancies. Promising results have been also reported when these conjugates are used in combination with conventional drugs. As RIPs have different intracellular substrates and are able to elicit more than one cell death pathway, they are considered very interesting pharmacological molecules for cancer therapy. Moreover, no drug resistance has been reported against these toxins.
Despite the knowledge of the ribosome-inactivating proteins being present for more than one century, many aspects of these plant molecules are still unclear and need to be better clarified. Among the issues requiring deeper investigations there are: i) the toxin-substrate interaction, especially with substrates other than ribosome, ii) the pathogenesis of cell damage, iii) the exact pathways of cell death triggered and iv) the pharmacokinetic and pharmacodynamic aspects in animal models.
Thus, the scope of this Frontiers Research Topic is to give the reader a comprehensive overview on the pharmacological potential of plant toxins, both as single agents or in combination strategies. Research articles, reviews and mini-reviews are welcome. In this Research Topic, we aim to collect studies, both in vitro and in vivo, concerning the structure, enzymatic activity, pharmacological properties and pathogenic mechanism of these plant toxins.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
Among plant toxins the most known are ribosome-inactivating proteins (RIPs), a family of enzymes widely spread in the plant kingdom, especially in angiosperms, but also present in some fungal and bacterial species.
RIPs are mainly classified as type 1, consisting of a single-chain protein with enzymatic activity, or type 2, consisting of an enzymatic A-chain linked by a disulfide bond to a lectin B-chain. The presence of the B-chain in type 2 RIPs makes them highly toxic for cells.
RIP activity was first identified as rRNA N-glycosylase (EC 3.2.2.22). RIPs specifically remove one adenine residue inside a GAGA sequence universally conserved among eukaryotic rRNA. Adenine removal damages ribosomes in an irreversible manner, causing inhibition of protein synthesis. RIPs are also able to deadenylate other substrates, such as DNA, mRNA, tRNA, and poly(A). For this reason, the enzymatic activity definition of these proteins has been proposed to be changed to polynucleotide: adenosine glycosylase.
RIPs have received much attention concerning their application in medicine. After linking to appropriate carriers, such as monoclonal antibodies (immunotoxins), these proteins have been used in experimental therapies to eliminate unwanted cells, responsible of pathological conditions, demonstrating particular efficacy against hematological malignancies. Promising results have been also reported when these conjugates are used in combination with conventional drugs. As RIPs have different intracellular substrates and are able to elicit more than one cell death pathway, they are considered very interesting pharmacological molecules for cancer therapy. Moreover, no drug resistance has been reported against these toxins.
Despite the knowledge of the ribosome-inactivating proteins being present for more than one century, many aspects of these plant molecules are still unclear and need to be better clarified. Among the issues requiring deeper investigations there are: i) the toxin-substrate interaction, especially with substrates other than ribosome, ii) the pathogenesis of cell damage, iii) the exact pathways of cell death triggered and iv) the pharmacokinetic and pharmacodynamic aspects in animal models.
Thus, the scope of this Frontiers Research Topic is to give the reader a comprehensive overview on the pharmacological potential of plant toxins, both as single agents or in combination strategies. Research articles, reviews and mini-reviews are welcome. In this Research Topic, we aim to collect studies, both in vitro and in vivo, concerning the structure, enzymatic activity, pharmacological properties and pathogenic mechanism of these plant toxins.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
