1. Kirkiin: A New Toxic Type 2 Ribosome-Inactivating Protein from the Caudex of Adenia kirkii .
- Author
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Bortolotti M, Maiello S, Ferreras JM, Iglesias R, Polito L, and Bolognesi A
- Subjects
- Antineoplastic Agents, Phytogenic isolation & purification, Antineoplastic Agents, Phytogenic toxicity, Cell Line, Tumor, Cell Survival drug effects, Erythrocyte Aggregation drug effects, Humans, Molecular Weight, Neuroblastoma metabolism, Neuroblastoma pathology, Protein Biosynthesis drug effects, Protein Synthesis Inhibitors isolation & purification, Protein Synthesis Inhibitors toxicity, Ribosome Inactivating Proteins, Type 2 isolation & purification, Ribosome Inactivating Proteins, Type 2 toxicity, Ribosomes drug effects, Ribosomes genetics, Ribosomes metabolism, Antineoplastic Agents, Phytogenic pharmacology, Neuroblastoma drug therapy, Passifloraceae enzymology, Protein Synthesis Inhibitors pharmacology, Ribosome Inactivating Proteins, Type 2 pharmacology
- Abstract
Ribosome-inactivating proteins (RIPs) are plant toxins that irreversibly damage ribosomes and other substrates, thus causing cell death. RIPs are classified in type 1 RIPs, single-chain enzymatic proteins, and type 2 RIPs, consisting of active A chains, similar to type 1 RIPs, linked to lectin B chains, which enable the rapid internalization of the toxin into the cell. For this reason, many type 2 RIPs are very cytotoxic, ricin, volkensin and stenodactylin being the most toxic ones. From the caudex of Adenia kirkii (Mast.) Engl., a new type 2 RIP, named kirkiin, was purified by affinity chromatography on acid-treated Sepharose CL-6B and gel filtration. The lectin, with molecular weight of about 58 kDa, agglutinated erythrocytes and inhibited protein synthesis in a cell-free system at very low concentrations. Moreover, kirkiin was able to depurinate mammalian and yeast ribosomes, but it showed little or no activity on other nucleotide substrates. In neuroblastoma cells, kirkiin inhibited protein synthesis and induced apoptosis at doses in the pM range. The biological characteristics of kirkiin make this protein a potential candidate for several experimental pharmacological applications both alone for local treatments and as component of immunoconjugates for systemic targeting in neurodegenerative studies and cancer therapy.
- Published
- 2021
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