On the role of proteasomes in cell biology and proteasome inhibition as a novel frontier in the development of immunosuppressants.
The proteasome, a large protease complex in cells, is the major machinery for protein degradation. It was previously considered a humble garbage collector, performing housekeeping duties to remove misfolded or spent proteins. Until recently, the interests of immunologists in proteasomes were focused largely on its role in antigen processing. Its real importance in cell biology has only been revealed contemporarily due to the availability of relatively specific inhibitors. It has now become increasingly clear that many aspects of immune responses highly depend on proper proteasome activity. Recently, a proteasome inhibitor has been successfully used to prevent acute as well as ongoing heart allograft rejection in mice. Such inhibitors are also efficacious in treating several autoimmune diseases, such as arthritis, psoriasis, and probably type I diabetes, in animal models. Phase II and III clinical trials of proteasome inhibitors in treating various tumors have shown promising results, and the side-effects of these drugs are tolerable. Therefore, proteasome inhibition represents a new and promising frontier in immunosuppressant development.
Wu
Jiangping
J
Laboratory of Transplantation Immunology, Nephrology Service of the Centre hospitalier de l'Université de Montréal, University of Montreal, Montreal, Canada. jianping.wu@umontreal.ca
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D009097:Multienzyme Complexes / Q000378:metabolism*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex; D013601:T-Lymphocytes / Q000276:immunology
D007166:Immunosuppressive Agents; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex