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This article addresses how quantitative models such as the one proposed in the companion article can be used to study cellular network perturbations such as knockdowns and pharmacological perturbations in a predictive manner. Using the kinetic model for cytosolic calcium dynamics in RAW 264.7 cells developed in the companion article, the calcium response to complement 5a (C5a) for the knockdown of seven proteins (C5a receptor; G-beta-2; G-alpha,i-2,3; regulator of G-protein signaling-10; G-protein coupled receptor kinase-2; phospholipase C beta-3; arrestin) is predicted and validated against the data from the Alliance for Cellular Signaling. The knockdown responses provide insights into how altered expressions of important proteins in disease states result in intermediate measurable phenotypes. Long-term response and long-term dose response have also been predicted, providing insights into how the receptor desensitization, internalization, and recycle result in tolerance. Sensitivity analysis of long-term response shows that the mechanisms and parameters in the receptor recycle path are important for long-term calcium dynamics. 相似文献
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Binding of serum response factor to cystic fibrosis transmembrane conductance regulator CArG-like elements, as a new potential CFTR transcriptional regulation pathway
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René C Taulan M Iral F Doudement J L'Honoré A Gerbon C Demaille J Claustres M Romey MC 《Nucleic acids research》2005,33(16):5271-5290
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Beischlag TV Taylor RT Rose DW Yoon D Chen Y Lee WH Rosenfeld MG Hankinson O 《The Journal of biological chemistry》2004,279(52):54620-54628
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水稻逆境相关转录因子研究进展 总被引:1,自引:0,他引:1
干旱、盐碱、高温和低温等逆境因子胁迫水稻的生长发育,进而影响水稻的产量和品质。因此,研究水稻的抗逆性,尤其是揭示其抗逆分子机理具有重要的生物学意义。近年来,水稻抗逆分子机理的研究主要集中在转录因子及其分子调控机制方面。在水稻中,目前研究较多的转录因子类型主要有b ZIP、MYB/MYC、WRKY、AP2/EREBP和NAC,它们的结构通常由DNA结合结构域、转录活化结构域、寡聚化位点和核定位信号组成。转录因子在水稻逆境信号转导途径中起着中心调节作用,它们将逆境信号传递和放大,通过与目的基因启动子区中顺式作用元件特异结合,调控下游多个逆境相关基因的表达,从而引起水稻对逆境应答反应,最终实现水稻获得综合抗逆性的提升。该文简要概述了植物转录因子的调控机制、结构特点、分类与功能特性,重点论述了转录因子在水稻抗逆中的作用,指出了转录因子应用过程中转基因水稻产生的负效应问题,并提出了解决负效应问题的研究思路,同时展望了今后转录因子的研究前景,以期为挖掘和应用新的水稻转录因子基因以及阐明其抗逆调控机制提供理论依据。 相似文献
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