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Research ArticleArticle

Evidence for Unique Calmodulin-Dependent Nuclear Factor-κB Regulation in WEHI-231 B Cells

Stuart D. Shumway, Craig M. Berchtold, Michael N. Gould and Shigeki Miyamoto
Molecular Pharmacology January 2002, 61 (1) 177-185; DOI: https://doi.org/10.1124/mol.61.1.177
Stuart D. Shumway
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Craig M. Berchtold
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Michael N. Gould
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Shigeki Miyamoto
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Abstract

Immature B cells express constitutive nuclear factor-κB (NF-κB) activity and inhibition of this activity is associated with the induction of apoptotic cell death. Previous studies have implicated a calcium-dependent proteolysis of the NF-κB inhibitory protein IκBα as critical in the maintenance of constitutive NF-κB activity in these cells. We tested whether modulation of diverse calcium-dependent processes affects the maintenance of constitutive NF-κB activity in the WEHI-231 immature B cell line. Calmodulin inhibitors, but not calcineurin inhibition, blocked both IκBα turnover and the maintenance of constitutive NF-κB activity. Inhibition of NF-κB DNA binding activity by the calmodulin antagonist W13 also resulted in a loss of the expression of the NF-κB target gene, IκBα. However, prolonged inhibition of NF-κB activity for up to 8 h did not lead to apoptotic induction in the WEHI-231 cells. Moreover, removal of calmodulin inhibitors resulted in the reappearance of constitutive NF-κB activity and the renewed expression of the IκBα gene. Thus, calmodulin activity is a requirement for the continual turnover of IκBα and the maintenance of constitutive NF-κB function in WEHI-231 cells. In addition, our findings suggest that inhibition of NF-κB activity does not lead to the immediate onset of apoptosis, indicating that prolonged inhibition of NF-κB–dependent gene expression is required to cause apoptosis of WEHI-231 B cells.

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Molecular Pharmacology: 61 (1)
Molecular Pharmacology
Vol. 61, Issue 1
1 Jan 2002
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Research ArticleArticle

Evidence for Unique Calmodulin-Dependent Nuclear Factor-κB Regulation in WEHI-231 B Cells

Stuart D. Shumway, Craig M. Berchtold, Michael N. Gould and Shigeki Miyamoto
Molecular Pharmacology January 1, 2002, 61 (1) 177-185; DOI: https://doi.org/10.1124/mol.61.1.177

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Research ArticleArticle

Evidence for Unique Calmodulin-Dependent Nuclear Factor-κB Regulation in WEHI-231 B Cells

Stuart D. Shumway, Craig M. Berchtold, Michael N. Gould and Shigeki Miyamoto
Molecular Pharmacology January 1, 2002, 61 (1) 177-185; DOI: https://doi.org/10.1124/mol.61.1.177
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