NF-κB1 and c-Rel cooperate to promote the survival of TLR4-activated B cells by neutralizing Bim via distinct mechanisms

被引：44

作者：

Banerjee, Ashish ^{[1
]}

Grumont, Raelene ^{[1
]}

Gugasyan, Raffi ^{[1
]}

White, Christine ^{[2
]}

Strasser, Andreas ^{[1
]}

Gerondakis, Steve ^{[1
]}

机构：

[1] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia

[2] Cleveland Clin, Dept Mol Genet, Cleveland, OH USA

来源：

BLOOD | 2008年 / 112卷 / 13期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1182/blood-2007-10-120832

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The nuclear factor-kappa B (NF-kappa B) pathway is crucial for the survival of B cells stimulated through Toll-like receptors (TLRs). Here, we show that the heightened death of TLR4-activated nfkb1(-/-) B cells is the result of a failure of the Tpl2/MEK/ERK pathway to phosphorylate the proapoptotic BH3-only protein Bim and target it for degradation. ERK inactivation of Bim after TLR4 stimulation is accompanied by an increase in A1/Bim and Bcl-x(L)/Bim complexes that we propose represents a c-Rel-dependent mechanism for neutralizing Bim. Together these findings establish that optimal survival of TLR4-activated B cells depends on the NF-kappa B pathway neutralizing Bim through a combination of Bcl-2 prosurvival protein induction and Tpl2/ERK-dependent Bim phosphorylation and degradation. (Blood. 2008; 112: 5063-5073)

引用

页码：5063 / 5073

页数：11

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