Mechanism of action of rapamycin: new insights into the regulation of G1-phase progression in eukaryotic cells.
The immunosuppressant drug, rapamycin (RAP), is a potent inhibitor of IL-2-dependent T-cell proliferation. The antiproliferative effect of RAP is mediated through the formation of an active complex with its cytosolic receptor protein, FKBP12. The molecular target of the FKBP12.RAP complex is a putative lipid kinase termed the mammalian Target Of Rapamycin (mTOR). This review will discuss recent findings suggesting that mTOR is a novel regulator of G1- to S-phase progression in eukaryotic cells.
Wiederrecht
G J
GJ
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Sabers
C J
CJ
Brunn
G J
GJ
Martin
M M
MM
Dumont
F J
FJ
Abraham
R T
RT
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D016213:Cyclins / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000187:drug effects* / Q000502:physiology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D016399:Lymphoma, T-Cell / Q000473:pathology; D008322:Mammals / Q000378:metabolism; D018448:Models, Immunological; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000502:physiology; D011090:Polyenes / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D016572:Cyclosporine; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011090:Polyenes; D011500:Protein Synthesis Inhibitors; D019893:Ribosomal Protein S6 Kinases; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; D016559:Tacrolimus; D022021:Tacrolimus Binding Proteins; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae