S. Meyer, N.Gail Kohler, A. Joly
Aug 18, 1997
Citations
2
Influential Citations
153
Citations
Quality indicators
Journal
FEBS Letters
Abstract
Cyclosporine A is an immunosuppressive agent that is used clinically in the prevention of transplant rejection and development of graft‐versus‐host disease. Recently, cyclosporine A has been shown to possess anti‐inflammatory properties and is capable of inhibiting lipopolysaccharide‐induced NF‐κB activation. Ubiquitin‐mediated proteasomal proteolysis plays a critical role in signal‐induced NF‐κB activation since it regulates both IκB degradation and p105 processing, it is also involved in the production of peptides for the assembly of MHC class I molecules. We report here that cylcosporine A acts as an uncompetitive inhibitor of the chymotrypsin‐like activity of the 20S proteasome in vitro and that it suppresses lipopolysaccharide‐induced IκB degradation and p105 processing in vivo demonstrating that inhibition of proteasome proteolysis is the mechanism by which cyclosporine A prevents NF‐κB activation. A structurally unrelated immunosuppressant, rapamycin, did not inhibit the 20S proteasome in vitro.