Mechanism of action of ricin and related toxins on the inactivation of eukaryotic ribosomes

  • Yaeta Endo
Part of the Cancer Treatment and Research book series (CTAR, volume 37)

Abstract

There is a group of cytotoxic proteins acting on eukaryotic ribosomes, including those from plants (ricin, abrin, and modeccin), fungi (α-sarcin), and bacteria (Shiga toxin). As discussed above by Olsnes, these toxins have been known to catalytically and irreversibly inactivate 60S ribosomal subunits affecting the activities of the peptide elongation reaction [also refer to 1,2]. However, the molecular mechanisms of their action have not been elucidated except for the case of α-sarcin, which has been known to hydrolyze a single phosphodiester bond between G-4325 and A-4326 in an evolutionarily conserved region of 28S rRNA [3–5]. Ricin and the other related toxins, e.g., abrin, modeccin, and Shiga toxin, consist of two peptide chains, A and B, linked together by disulfide bonds, while α-sarcin is a single peptide [6]. The B chain binds the toxins to receptors on the cell surface, and the A chain enters the cytoplasm and inactivates the 60S ribosomal subunits. Irrespective of the structural differences, the mode of action of ricin and the related toxins is known to be identical with that of α-sarcin in the following aspects: 1) They affect EF-1 and EF-2 associated functions of 60S subunits, and 2) they do not require energy or any cofactors. These lines of evidence suggested to us that like α-sarcin they also act on rRNA rather than on ribosomal proteins in 60S ribosomal subunits. The possibility that the toxins are endonucleases was once ruled out in 1976 by Mitchell et al. [7], who reported that ricin does not change the sizes of any rRNA species of L-cell polysomes in vitro, but more recently it was suggested by Obrig et al. [8], who demonstrated that the toxins, ricin, phytolaccin, and Shiga toxin are able to hydrolyze naked 5S and 5.8S rRNAs.

Keywords

Hydrolysis Migration Aniline Adenine Ethidium 

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© Kluwer Academic Publishers 1988

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  • Yaeta Endo

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