BCL10 is required for NF-κB nuclear translocation by both canonical and non-canonical pathways and for NF-κB-inducing kinase (NIK) phosphorylation
B-cell CLL/lymphoma 10 (BCL10), the caspase recruitment domain (CARD)-containing protein involved in the etiology of the mucosa-associated lymphoid tissue (MALT) lymphomas, has been implicated in inflammatory processes in epithelial cells, as well as in immune cells. Experiments in this report indicate that BCL10 is required for activation of Nuclear Factor (NF)-κB by both canonical and non-canonical pathways, following stimulation by the sulfated polysaccharide carrageenan (CGN). In WT and IkappaB-kinase (IKK)α-/- mouse embryonic fibroblasts, increases in phospho-IκBα, nuclear NF-κB p65 (RelA) and p50, and KC, the mouse analog of human IL-8, were markedly reduced by silencing BCL10 or by exposure to the free radical scavenger Tempol. In IKKβ-/- cells, BCL10 silencing, but not Tempol, reduced the CGN-induced increases in KC, phospho-NF-κB-inducing kinase (NIK), cytoplasmic NF-κBp100, and nuclear NF-κBp52 and RelB, suggesting a BCL10 requirement for activation of the non-canonical pathway. In NCM460 cells, derived from normal, human colonic epithelium, the CGN-induced increases in NF-κB family members, p65, p50, p52, and RelB, were inhibited by BCL10 silencing. Although ELISA and confocal images demonstrated no change in total NIK following CGN, increases in phospho-NIK in the WT, IKKα-/- and IKKβ-/- cells were inhibited by silencing BCL10. These findings indicate an upstream signaling role for BCL10, in addition to its effects on IKKγ, the regulatory component of the IKK signalosome, and a requirement for BCL10 in both canonical and non-canonical pathways of NF-κB activation. Also, the commonly used food additive carrageenan can be added to the short list of known activators of both pathways.
Bhattacharyya S, Borthakur A, Tyagi S, Gill R, Chen ML, Dudeja PK, Tobacman JK. BCL10 is required for NF-κB nuclear translocation by both canonical and non-canonical pathways and for NF-κB-inducing kinase (NIK) phosphorylation. Journal of Biological Chemistry. 2009 Nov 6:jbc-M109.