Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice.
A20 is a cytoplasmic zinc finger protein that inhibits nuclear factor kappaB (NF-kappaB) activity and tumor necrosis factor (TNF)-mediated programmed cell death (PCD). TNF dramatically increases A20 messenger RNA expression in all tissues. Mice deficient for A20 develop severe inflammation and cachexia, are hypersensitive to both lipopolysaccharide and TNF, and die prematurely. A20-deficient cells fail to terminate TNF-induced NF-kappaB responses. These cells are also more susceptible than control cells to undergo TNF-mediated PCD. Thus, A20 is critical for limiting inflammation by terminating TNF-induced NF-kappaB responses in vivo.
Lee
E G
EG
Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC 6084, Chicago, IL 60637, USA.
Boone
D L
DL
Chai
S
S
Libby
S L
SL
Chien
M
M
Lodolce
J P
JP
Ma
A
A
D000818:Animals; D017209:Apoptosis; D002100:Cachexia / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D018390:Gene Targeting; D020672:I-kappa B Proteins; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D007375:Interleukin-1 / Q000494:pharmacology; D007422:Intestines / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000473:pathology; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D009687:Nuclear Proteins; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse