PMID: 8594303Jan 1, 1996Paper

Mechanism of action of the immunosuppressant rapamycin

Life Sciences
F J Dumont, Q Su

Abstract

Rapamycin has potent immunosuppressive properties reflecting its ability to disrupt cytokine signaling that promotes lymphocyte growth and differentiation. In IL-2-stimulated T cells, rapamycin impedes progression through the G1/S transition of the proliferation cycle, resulting in a mid-to-late G1 arrest. Two major biochemical alterations underlie this mode of action. The first one affects the phosphorylation/activation of the p70 S6 kinase (p70s6k), an early event of cytokine-induced mitogenic response. By inhibiting this enzyme, whose major substrate is the 40S ribosomal subunit S6 protein, rapamycin reduces the translation of certain mRNA encoding for ribosomal proteins and elongation factors, thereby decreasing protein synthesis. A second, later effect of rapamycin in IL-2-stimulated T cells is an inhibition of the enzymatic activity of the cyclin-dependent kinase cdk2-cyclin E complex, which functions as a crucial regulator of G1/S transition. This inhibition results from a prevention of the decline of the p27 cdk inhibitor, that normally follows IL-2 stimulation. To mediate these biochemical alterations, rapamycin needs to bind to intracellular proteins, termed FKBP, thereby forming a unique effector molecular complex. H...Continue Reading

References

Feb 1, 1977·Canadian Journal of Physiology and Pharmacology·R R MartelS Galet
Feb 1, 1992·Transplantation·A FrancavillaS L Schreiber
Mar 3, 1992·Biochemistry·A GalatS L Schreiber
Jan 1, 1992·Annual Review of Immunology·N H Sigal, F J Dumont
Apr 1, 1992·Current Opinion in Genetics & Development·P K Brindle, M R Montminy
Dec 11, 1992·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C C TrandinhM H Saier
Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S FerrariG Thomas
May 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A FrancavillaQ H Zeng
Jan 1, 1992·Annual Review of Immunology·A MiyajimaK Arai
Aug 1, 1992·Clinical and Experimental Immunology·W L BaederL M Adams
Feb 1, 1991·European Journal of Immunology·B E BiererS J Burakoff
Jul 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·T HultschR J Hohman
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·B E BiererS L Schreiber
Nov 1, 1990·Immunology Today·L A O'NeillJ Saklatvala
Jan 1, 1990·Annual Review of Immunology·C Esser, A Radbruch
Oct 1, 1984·The Journal of Antibiotics·C P EngC Vézina
Feb 1, 1994·Journal of Leukocyte Biology·A D Keegan, J H Pierce
Jul 1, 1994·Cellular Immunology·K M Aagaard-Tillery, D F Jelinek
Aug 30, 1994·Biochemical and Biophysical Research Communications·Y ChenK L Molnar-Kimber
Oct 1, 1994·European Journal of Immunology·S Y PaiB E Bierer

❮ Previous
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Citations

Aug 19, 2010·Cell Biochemistry and Biophysics·Mercedes Pozuelo-RubioCarol Mackintosh
Jul 2, 2009·Journal of Chemical Biology·Lisa M Ballou, Richard Z Lin
Mar 12, 2004·Transplantation Proceedings·V StadlbauerK H Tscheliessnigg
Jul 1, 2010·The Journal of Antibiotics·Sung Ryeol ParkYeo Joon Yoon
Oct 3, 2002·Journal of Neurochemistry·Lydie GuermonprezYvette Morot-Gaudry-Talarmain
Apr 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Luciana Madeira da SilvaStephen M Beverley
Sep 3, 2011·Rejuvenation Research·Sven Bulterijs
Sep 16, 2008·European Heart Journal·Sudhir S KushwahaJeffrey L Platt
Oct 6, 2000·Clinical Neuropharmacology·P B RosenbergS I Deutsch
Dec 23, 2004·Transplant International : Official Journal of the European Society for Organ Transplantation·Markus GubaEdward K Geissler
May 17, 2000·The Journal of Clinical Investigation·M L BoytimC Clayberger
Apr 9, 2013·PloS One·Jean-Paul DecuypereJan B Parys
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Krishna KadaveruMartin R Schiller
Mar 24, 2011·Future Medicinal Chemistry·Abhijit RoychowdhurySanjay Kumar
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·I M ConboyP P Jones
Jan 16, 2016·Cancers·Laura L Stafman, Elizabeth A Beierle
Apr 29, 2015·Expert Opinion on Drug Safety·Jost KlawitterUwe Christians
Mar 15, 2005·Transplant Infectious Disease : an Official Journal of the Transplantation Society·O ThaunatH Kreis
Jul 25, 2007·Journal of Neurochemistry·Hanoch KaphzanKobi Rosenblum
May 12, 2006·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A MercalliL Piemonti
Oct 9, 2014·Immunological Investigations·Orla MaguireHans Minderman
Jul 5, 2005·Expert Opinion on Investigational Drugs·J Staunton, B Wilkinson
Oct 21, 2011·Expert Opinion on Investigational Drugs·Bruno VincenziGiuseppe Tonini
Jun 7, 2006·Leukemia & Lymphoma·Yasuhiro MaedaAkihisa Kanamaru
Jul 6, 2010·Biochemical and Biophysical Research Communications·Chuan-Xiu BianBing-Hua Jiang

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