NF-kappa B1 and c-Rel cooperate to promote the survival of TLR4-activated B cells by neutralizing Bim via distinct mechanisms

Author(s): Banerjee, A; Grumont, R; Gugasyan, R; White, C; Strasser, A; Gerondakis, S;
Details: Publication Year 2008-12-15,Volume 112,Issue #13,Page 5063-5073
Journal Title: BLOOD
Publication Type: Journal Article
Abstract: 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)
Publisher: AMER SOC HEMATOLOGY
Keywords: NF-KAPPA-B; BH3-ONLY PROTEIN BIM(EL); REGULATED KINASES 1/2; FAMILY-MEMBER BIM; BCL-2 FAMILY; TRANSCRIPTION FACTORS; SIGNALING PATHWAYS; HEMATOPOIETIC COMPARTMENT; MACROPHAGE APOPTOSIS; CYCLE PROGRESSION
Publisher's Version: https://doi.org/10.1182/blood-2007-10-120832
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Creation Date: 2008-12-15 12:00:00