Publication Date:
2007-08-04
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carmody, Ruaidhri J -- Ruan, Qingguo -- Palmer, Scott -- Hilliard, Brendan -- Chen, Youhai H -- AI069289/AI/NIAID NIH HHS/ -- AI50059/AI/NIAID NIH HHS/ -- DK070691/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):675-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673665" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Line
;
Cells, Cultured
;
DNA/metabolism
;
Female
;
Half-Life
;
Immune Tolerance
;
Immunity, Innate
;
Lipopolysaccharides/immunology
;
Macrophage Activation
;
Macrophages, Peritoneal/*immunology/metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
;
NF-kappa B p50 Subunit/*metabolism
;
Promoter Regions, Genetic
;
Proto-Oncogene Proteins/genetics/*metabolism
;
*Signal Transduction
;
Toll-Like Receptors/*metabolism
;
Transcription Factor RelA/metabolism
;
Transcription Factors/genetics/*metabolism
;
Transcription, Genetic
;
Tumor Necrosis Factor-alpha/genetics/metabolism
;
Ubiquitin/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
