| First Author | Banerjee A | Year | 2008 |
| Journal | Blood | Volume | 112 |
| Issue | 13 | Pages | 5063-73 |
| PubMed ID | 18805964 | Mgi Jnum | J:143616 |
| Mgi Id | MGI:3828244 | Doi | 10.1182/blood-2007-10-120832 |
| Citation | Banerjee A, et al. (2008) NF-kappaB1 and c-Rel cooperate to promote the survival of TLR4-activated B cells by neutralizing Bim via distinct mechanisms. Blood 112(13):5063-73 |
| abstractText | The nuclear factor-kappaB (NF-kappaB) 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 Tpl(2)/MEK/ERK pathway to phosphorylate the proapo-ptotic 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-kappaB pathway neutralizing Bim through a combination of Bcl-2 prosurvival protein induction and Tpl2/ERK-dependent Bim phosphorylation and degradation. |
