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ABSTRACT:
Ribosome-inactivating proteins (RIPs) are toxins that are capable to permanently inhibit the synthesis of protein. RIP type II is a heterodimeric protein consisting of an A subunit linked to a lectin-like B chain by a disulfide bridge. Ricin contained in the seeds of Ricinus communis L. is a type II RIP which possesses cytotoxicity activity. However, due to the non-selectivity of the B-lectin chain, ricin needs delivering-vehicles to enhance its cytotoxicity. This article is devoted to reviewing the anticancer activity of ricin in castor bean seeds (a plant type II RIPs) and its various types of cytotoxicity enhancers.
KEYWORDS: apoptosis, autophagy, lectin, Ribosome-inactivating protein.
INTRODUCTION:
Ribosome-inactivating proteins (RIPs) are toxins that are apt to permanently inhibit the translation or the synthesis of protein. These proteins are widely distributed in nature, particularly in plants. RIPs in plants are categorized into three types: (i) Type I, composed of a single polypeptide chain (monomeric protein) of approximately 30 kDa, consists of an Nterminal, an active domain, and a C-terminal (1); (ii) Type II is a heterodimeric protein consisting of an A chain (an N-terminal and an active domain, functionally equivalent to the type I polypeptide), linked to a lectinlike B chain by a disulfide bridge, and a C-terminal1.
The lectin binds to glycoproteins or glycolipids to promote a toxin-endocytosis that leads to its higher toxicity compared to the type I2,3 (iii) Type III consists of an N-terminal domain closely related to the A chain of RIPs and linked to an unrelated C-terminal domain with unknown function4. In cell walls or membranes, lectin binds to sugar moieties and thus alters the physiology of the membrane to induce cell agglutination, mitosis, or other biochemical changes5.
RIPs are officially defined as rRNA N-glycosidases (EC 3.2.2.22). These proteins catalytically inactivate eukaryotic and prokaryotic ribosomes, and selectively break the bond between adenine and ribose from the universally conserved a-sarcin/ricin loop (SRL) (Figure 1) of the large rRNA4,2. The SRL is a highly conserved sequence found in the RNA of all large ribosomal subunits. The structural stability of the SRL is constructed mostly by n-n interactions. Removal of the key adenine at the terminal of the loop by cytotoxins can destabilize this interaction6. The SRL is an assembly of two secondary structure...