RT Journal Article
SR Electronic
T1 Evidence for Unique Calmodulin-Dependent Nuclear Factor-κB Regulation in WEHI-231 B Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 177
OP 185
DO 10.1124/mol.61.1.177
VO 61
IS 1
A1 Stuart D. Shumway
A1 Craig M. Berchtold
A1 Michael N. Gould
A1 Shigeki Miyamoto
YR 2002
UL http://molpharm.aspetjournals.org/content/61/1/177.abstract
AB 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.