Induction of cell cycle arrest in lymphocytes by Actinobacillus actinomycetemcomitans cytolethal distending toxin requires three subunits for maximum activity.

摘要: We have previously shown that Actinobacillus actinomycetemcomitans produces an immunosuppressive factor encoded by the cytolethal distending toxin ( cdt ) B gene. In this study, we used rCdt peptides to study contribution of each subunit activity. As reported, CdtB is only Cdt capable inducing cell cycle arrest itself. Although CdtA and CdtC do not exhibit activity alone, able significantly enhance ability induce G 2 in Jurkat cells; these effects were dependent upon protein concentration. Moreover, combined addition both increased ED 50 for >7000-fold. another series experiments, demonstrate three are form a functional unit on surface. However, interactions first require complex forms between subunits, indicating required interaction holotoxin. This conclusion further supported experiments which cells normal human lymphocytes protected from holotoxin-induced pre-exposure CdtC. Finally, optical biosensor technology show strong affinity one (10 −7 M). Furthermore, although unable bind either or it forming stable with CdtA/CdtC. The implications our results respect function structure holotoxin discussed.