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Crossregulation of NF-κB by the APC/GSK-3β/β-catenin pathway

Authors

  • Jiong Deng,

    1. Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Weiya Xia,

    1. Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Stephanie A. Miller,

    1. Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas
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  • Yong Wen,

    1. Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas
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  • Hong-Ying Wang,

    1. Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Mien-Chie Hung

    Corresponding author
    1. Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas
    • Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
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Abstract

Glycogen synthase kinase-3β (GSK-3β) and adenomatous polyposis coli (APC) play an important role in the regulation of β-catenin. Inhibition of or defects in their functions can lead to activation of β-catenin. β-catenin has been recently found to interact with and inhibit nuclear factor kappa B (NF-κB). However, the regulatory roles of GSK-3β/APC on the NF-κB signaling pathway are unknown because of their diverse effects. In this study, we investigated whether GSK-3β/APC might regulate NF-κB activity through β-catenin. We found that inhibition of GSK-3β suppressed NF-κB activity, whereas reexpression of APC restored NF-κB activity in APC mutated cells. The regulatory effects were through β-catenin because depletion of β-catenin with small interfering RNA (siRNA) in the same systems reversed the effects. The regulatory relationship was further supported by the analysis of primary breast tumor tissues in vivo in which NF-κB target TRAF1 was inversely correlated with activated β-catenin. Thus, APC/GSK-3β, through β-catenin, may crossregulate NF-κB signaling pathway. © 2004 Wiley-Liss, Inc.

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