Proteolytic pathways involved in modulation of CD20 levels.
Recent observations indicate that rituximab-resistant lymphoma cells exhibit upregulation of components of the ubiquitin-proteasome system (UPS). Therefore, proteasome inhibitors including the clinically approved bortezomib might influence the levels of CD20, a rituximab target antigen. We observed that incubation of tumor cells with rituximab leads to increased levels of ubiquitinated CD20. However, inhibition of the UPS is not associated with upregulation, but rather with a counterintuitive downregulation of surface CD20 levels that increases resistance of tumor cells to rituximab-mediated cytotoxicity. Although preliminary observations indicate that CD20 might be a substrate for two proteolytic systems, the mechanisms as well as significance of these findings require further studies.
Winiarska
Magdalena
M
Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, Warsaw, Poland.
Bil
Jacek
J
Nowis
Dominika
D
Golab
Jakub
J
D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D018951:Antigens, CD20 / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007167:Immunotherapy; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D000069283:Rituximab; D054875:Ubiquitination / Q000187:drug effects
D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D004791:Enzyme Inhibitors; D061988:Proteasome Inhibitors; D000069283:Rituximab; D046988:Proteasome Endopeptidase Complex