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We recently found that aralin, a novel cytotoxic protein consisting of two subunits, from  Aralia elata  selectively induces apoptosis in transformed cells as compared to normal cells. Here we report that aralin is a lectin specific for galactose (Gal) and its derivatives, and possesses RNA  N -glycosidase activity as a new type II ribosome-inactivating protein (RIP). The RNA  N -glycosidase activity of aralin was detected in cell-free and whole cell systems by the generation of an R-fragment from 28S rRNA. Coinciding with appearance of the R-fragment in aralin-treated cells, significant inhibition of protein synthesis was observed prior to the onset of apoptosis. Aralin-evoked cell death was efficiently repressed by the addition of Gal and its derivatives. Interestingly, melibiose preferentially protected normal cells from apoptosis as compared with transformed cells. Using rhodamine-coupled aralin, the aralin receptor could be clearly detected around the cell surface of transformed cells, but to a lesser extent on normal cells. Receptor binding was suppressed by Gal. These results indicate that aralin is incorporated into cells via its Gal-containing cell surface receptor and induces apoptosis through its RIP activity. Moreover, the expression level and/or structural changes of the aralin receptor may affect the sensitivity toward aralin.

An apoptotic inducer, aralin, is a novel type II ribosome-inactivating protein from Aralia elata