| First Author | Carmody RJ | Year | 2007 |
| Journal | Science | Volume | 317 |
| Issue | 5838 | Pages | 675-8 |
| PubMed ID | 17673665 | Mgi Jnum | J:123417 |
| Mgi Id | MGI:3718281 | Doi | 10.1126/science.1142953 |
| Citation | Carmody RJ, et al. (2007) Negative regulation of toll-like receptor signaling by NF-kappaB p50 ubiquitination blockade. Science 317(5838):675-8 |
| abstractText | Toll-like receptors (TLRs) trigger the production of inflammatory cytokines and shape adaptive and innate immunity to pathogens. We report the identification of B cell leukemia (Bcl)-3 as an essential negative regulator of TLR signaling. By blocking ubiquitination of p50, a member of the nuclear factor (NF)-kappaB family, Bcl-3 stabilizes a p50 complex that inhibits gene transcription. As a consequence, Bcl-3-deficient mice and cells were found to be hypersensitive to TLR activation and unable to control responses to lipopolysaccharides. Thus, p50 ubiquitination blockade by Bcl-3 limits the strength of TLR responses and maintains innate immune homeostasis. These findings indicate that the p50 ubiquitination pathway can be selectively targeted to control deleterious inflammatory diseases. |
