[FK506 - binding proteins in the regulation of transcription factors activity in T cells].
Members of the FKBP family play various functions within the cell. For T cell biology essential is their involvement in the regulation of cytokine genes transcription, mainly at the level of nucleocytoplasmic transport of transcription factors. FKBP12 is the mediator of immunosuppressive action of FK506. When complexed with the drug, FKBP12 blocks nuclear import of NFAT and formation of AP-1 heterodimer, due to inhibition of calcium-dependent phosphatase calcineurin and JNK/p38 pathways. Suppression of these two, and possibly some other signaling pathways leads to prevention of IL-2 expression and T cell activation. FKBP51 and FKBP52 are natural components of glucocorticoid receptor complex and direct regulators of its activity. Upon ligand binding FKBP51, maintaining receptor in the cytoplasm, is exchanged by FKBP52, which allows translocation of the complex to the nucleus. Thereby FKBPs take a part in the regulation of immune response by glucocorticoids.
Kochel
Izabela
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Zakład Immunologii Nowotworów, Instytut Immunologii i Terapii Doświadczalnej PAN im. L. Hirszfelda we Wrocławiu.
Strzadała
Leon
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D021581:Active Transport, Cell Nucleus; D019703:Calcineurin; D016207:Cytokines / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D022021:Tacrolimus Binding Proteins / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D016207:Cytokines; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D019703:Calcineurin; D022021:Tacrolimus Binding Proteins