Molecular mechanisms of immunosuppressive agents.
Recent data on the molecular mechanism of some immunosuppressive drugs provide strong support for the fascinating postulate that CSA and FK506 work by binding to immunophilins and then, as a drug-immunophilin complex, inhibiting the calcium-activated protein phosphatase, calcineurin. This inhibition could result in an altered modification pattern of the cytoplasmic components of transcription factors, thereby disturbing their nuclear translocation, which is a prerequisite for proper IL-2 transcription. It looks as if, with the immunosuppressive microbial metabolites as molecular probes, the pieces of this complex signal transduction puzzle are starting to fit together! Once the details of the chain of events along the T-cell signaling pathways are known, the molecular structures involved will provide new tools to be used in the search for and the rational design of new and improved therapeutic agents.
Borel
J F
JF
Université de Berne-Suisse.
Baumann
G
G
D000591:Amino Acid Isomerases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D018833:Chaperonins / Q000378:metabolism; D016572:Cyclosporine / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D019696:Peptidylprolyl Isomerase; D011090:Polyenes / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus; D016559:Tacrolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D011090:Polyenes; D016572:Cyclosporine; D011505:Protein-Tyrosine Kinases; D004706:Endodeoxyribonucleases; D018833:Chaperonins; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus; D016559:Tacrolimus