Intracellular transport and cytotoxicity of the protein toxin ricin
Natalia Sowa-Rogozińska , Hanna Sominka , Jowita Nowakowska-Gołacka , Kirsten Sandvig , Monika Słomińska-Wojewódzka
AbstractRicin can be isolated from the seeds of the castor bean plant (Ricinus communis). It belongs to the ribosome-inactivating protein (RIP) family of toxins classified as a bio-threat agent due to its high toxicity, stability and availability. Ricin is a typical A-B toxin consisting of a single enzymatic A subunit (RTA) and a binding B subunit (RTB) joined by a single disulfide bond. RTA possesses an RNA N-glycosidase activity; it cleaves ribosomal RNA leading to the inhibition of protein synthesis. However, the mechanism of ricin-mediated cell death is quite complex, as a growing number of studies demonstrate that the inhibition of protein synthesis is not always correlated with long term ricin toxicity. To exert its cytotoxic effect, ricin A-chain has to be transported to the cytosol of the host cell. This translocation is preceded by endocytic uptake of the toxin and retrograde traffic through the trans-Golgi network (TGN) and the endoplasmic reticulum (ER). In this article, we describe intracellular trafficking of ricin with particular emphasis on host cell factors that facilitate this transport and contribute to ricin cytotoxicity in mammalian and yeast cells. The current understanding of the mechanisms of ricin-mediated cell death is discussed as well. We also comment on recent reports presenting medical applications for ricin and progress associated with the development of vaccines against this toxin.
|Journal series||Toxins, ISSN 2072-6651, (N/A 100 pkt)|
|Publication size in sheets||1.8|
|Keywords in English||ricin, protein synthesis inhibition, apoptosis|
|License||Journal (articles only); published final; ; with publication|
|Score||= 100.0, 28-01-2020, ArticleFromJournal|
|Publication indicators||= 2; : 2017 = 1.136; : 2018 = 3.895 (2) - 2018=4.009 (5)|
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