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name: Rate Law for Rec dependent transcription of TBet
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reaction: 750038
reaction: 750023
reaction: 750042
reaction: 750022
reaction: 750026
function def: 750094
creator:
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    orgname: Humboldt Universität
  n:
    given: Edda
    family: Schulz
reaction: 750045
name: Rate Law for Tbet IFNg dependent transcription
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length unit: length
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occurs in: http://identifiers.org/taxonomy/10090
created:
  W3 CDTF: Wed Jun 10 15:32:34 BST 2009
species: 750016
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creator:
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  n:
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    family: Chelliah
function def: 750086
function def: 750091
name: Translation rate law
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reaction: 750021
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modified:
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notes: This a model from the article: Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. Schulz EG, Mariani L, Radbruch A, Höfer T. Immunity. 2009;30(5):666-8. 19409816 , Abstract: Differentiation of naive T lymphocytes into type I T helper (Th1) cells requires interferon-gamma and interleukin-12. It is puzzling that interferon-gamma induces the Th1 transcription factor T-bet, whereas interleukin-12 mediates Th1 cell lineage differentiation. We use mathematical modeling to analyze the expression kinetics of T-bet, interferon-gamma, and the IL-12 receptor beta2 chain (IL-12Rbeta2) during Th1 cell differentiation, in the presence or absence of interleukin-12 or interferon-gamma signaling. We show that interferon-gamma induced initial T-bet expression, whereas IL-12Rbeta2 was repressed by T cell receptor (TCR) signaling. The termination of TCR signaling permitted upregulation of IL-12Rbeta2 by T-bet and interleukin-12 signaling that maintained T-bet expression. This late expression of T-bet, accompanied by the upregulation of the transcription factors Runx3 and Hlx, was required to imprint the Th cell for interferon-gamma re-expression. Thus initial polarization and subsequent imprinting of Th1 cells are mediated by interlinked, sequentially acting positive feedback loops of TCR-interferon-gamma-Stat1-T-bet and interleukin-12-Stat4-T-bet signaling. The original model was created by: Edda G. Schulz schulz@drfz.de Theoretical Biophysics, Institute of Biology, Humboldt Universität, Invalidenstrasse 42, 10115 Berlin, Germany. This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team. For more information see the terms of use . To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Cen…
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