Epidermal growth factor activation of NF-κB is mediated through IκBα degradation and intracellular free calcium (original) (raw)

Oncogene volume 16, pages 2095–2102 (1998)Cite this article

Abstract

The transcription factor NF-κB is normally sequestered in the cytoplasm by its inhibitory subunit IκB. Most extracellular signals activate NF-κB through a mechanism involving the phosphorylation and proteasome-dependent degradation of IκB. EGF activates NF-κB in A-431 carcinoma cells, which overexpress EGF receptors and in mouse embryo fibroblasts, which have a normal complement of receptors. Supershift experiments indicate that the NF-κB complexes induced by EGF are composed of p50/p50 homodimers and p65/p50 heterodimers, but not c-rel. EGF stimulation enhances the degradation of IκBα, but not IκBβ nor an N-terminal deletion mutant of IκBα. Treatment of cells with a proteasome inhibitor, such as ALLN or MG132, blocks EGF-mediated NF-κB activation, indicating that EGF-induced NF-κB activation requires proteasome-dependent IκB degradation. Also, Bapta A/M (a cell-permeable chelator of intracellular calcium) blocks EGF-induced NF-κB activation and IκBα degradation, suggesting a requirement of intracellular free Ca2+ for this growth factor response. Protein kinase C inhibition, in contrast, did not influence EGF activation of NF-κB.

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Authors and Affiliations

  1. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, 37232-0146, Tennessee, USA
    Lei Sun & Graham Carpenter
  2. Department of Medicine, Vanderbilt University School of Medicine, Nashville, 37232-0146, Tennessee, USA
    Graham Carpenter
  3. Department of Oncology, Norvatis Pharmaceutical Corp., East Hanover, 07936, NJ
    Lei Sun

Authors

  1. Lei Sun
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  2. Graham Carpenter
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Sun, L., Carpenter, G. Epidermal growth factor activation of NF-κB is mediated through IκBα degradation and intracellular free calcium.Oncogene 16, 2095–2102 (1998). https://doi.org/10.1038/sj.onc.1201731

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