Rapid degradation of the complement regulator, CD59, by a novel inhibitor

Abstract

Background: Surface expression of complement inhibitors, such as the glycosylphosphatidylinositol-anchored protein CD59, prevent complement-dependent lysis of cancer cells. Results: The non-toxic domain-4 of the bacterial toxin intermedilysin (rILYd4) blocks CD59 complement inhibitory activity. Conclusion: rILYd4 induces CD59 internalization and rapid degradation in lysosomes in non-small lung carcinoma cells. Significance: CD59 serves as a model for glycosylphosphatidylinositol-anchored protein trafficking and rILYd4 shows potential for immunotherapy. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.