Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Carrier Proteins / antagonists & inhibitors*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Carrier Proteins / physiology
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Cell Cycle Proteins
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Cloning, Molecular
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Cyclins / metabolism
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Cyclosporine / pharmacology
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DNA, Complementary / genetics
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DNA-Binding Proteins / metabolism*
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Eukaryotic Cells / drug effects*
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Eukaryotic Cells / physiology
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Fungal Proteins / antagonists & inhibitors
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Fungal Proteins / genetics
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Fungal Proteins / physiology
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G1 Phase / drug effects*
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G1 Phase / physiology
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Heat-Shock Proteins / metabolism*
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Immunosuppressive Agents / pharmacology*
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Interleukin-2 / antagonists & inhibitors
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Interleukin-2 / pharmacology
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Interleukin-2 / physiology
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Lymphocyte Activation / drug effects
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Lymphoma, T-Cell / pathology
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Mammals / metabolism
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Models, Immunological
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Phosphatidylinositol 3-Kinases*
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
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Phosphotransferases (Alcohol Group Acceptor) / physiology
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Polyenes / pharmacology*
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Protein Synthesis Inhibitors / pharmacology
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Ribosomal Protein S6 Kinases / antagonists & inhibitors
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Ribosomal Protein S6 Kinases / physiology
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Saccharomyces cerevisiae / cytology
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae Proteins*
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Sirolimus
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects
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Tacrolimus / pharmacology
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Tacrolimus Binding Proteins
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Tumor Cells, Cultured
Substances
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Carrier Proteins
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Cell Cycle Proteins
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Cyclins
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DNA, Complementary
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DNA-Binding Proteins
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Fungal Proteins
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Heat-Shock Proteins
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Immunosuppressive Agents
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Interleukin-2
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Polyenes
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Protein Synthesis Inhibitors
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Saccharomyces cerevisiae Proteins
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Cyclosporine
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Phosphotransferases (Alcohol Group Acceptor)
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TOR1 protein, S cerevisiae
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TOR2 protein, S cerevisiae
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Ribosomal Protein S6 Kinases
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Tacrolimus Binding Proteins
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Sirolimus
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Tacrolimus