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PMID: 11009421 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice.

Science (New York, N.Y.) ·Vol. 289 ·No. 5488 ·2000-09-29 ·Pages 2350-4

Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A

Abstract

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.

MeSH Terms
Animals Apoptosis Cachexia/pathology,physiopathology Cells, Cultured Cysteine Endopeptidases DNA/metabolism DNA-Binding Proteins/genetics,metabolism Fibroblasts/metabolism Gene Targeting I-kappa B Proteins Inflammation/pathology,physiopathology Interleukin-1/pharmacology Intestines/pathology Intracellular Signaling Peptides and Proteins Kidney/pathology Lipopolysaccharides/immunology Liver/pathology Mice NF-KappaB Inhibitor alpha NF-kappa B/metabolism Nuclear Proteins Phosphorylation Proteins/genetics,physiology Skin/pathology T-Lymphocytes/cytology,metabolism Tumor Necrosis Factor alpha-Induced Protein 3 Tumor Necrosis Factor-alpha/pharmacology Zinc Fingers
Chemicals
DNA-Binding Proteins I-kappa B Proteins Interleukin-1 Intracellular Signaling Peptides and Proteins Lipopolysaccharides NF-kappa B Nfkbia protein, mouse Nuclear Proteins Proteins Tumor Necrosis Factor-alpha NF-KappaB Inhibitor alpha DNA Tumor Necrosis Factor alpha-Induced Protein 3 Cysteine Endopeptidases Tnfaip3 protein, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lee E G
Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC 6084, Chicago, IL 60637, USA.
Boone D L
Chai S
Libby S L
Chien M
Lodolce J P
Ma A
References (18)
18 references, click to expand
  1. The A20 zinc finger protein protects cells from tumor necrosis factor cytotoxicity.
    J Biol Chem. 1992 Jun 25;267(18):12424-7 PMID: 1618749
  2. NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway.
    Science. 1993 Mar 26;259(5103):1912-5 PMID: 8096091
  3. Fas antigen and p55 TNF receptor signal apoptosis through distinct pathways.
    J Immunol. 1994 Feb 15;152(4):1751-5 PMID: 7509828
  4. Lymphoid expression and regulation of A20, an inhibitor of programmed cell death.
    J Immunol. 1995 Feb 15;154(4):1699-706 PMID: 7836754
  5. Constitutive NF-kappa B activation, enhanced granulopoiesis, and neonatal lethality in I kappa B alpha-deficient mice.
    Genes Dev. 1995 Nov 15;9(22):2736-46 PMID: 7590249
  6. The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation.
    Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6721-5 PMID: 8692885
  7. A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism.
    J Biol Chem. 1996 Jul 26;271(30):18068-73 PMID: 8663499
  8. Severe liver degeneration and lack of NF-kappaB activation in NEMO/IKKgamma-deficient mice.
    Genes Dev. 2000 Apr 1;14(7):854-62 PMID: 10766741
  9. Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation.
    Immunity. 2000 Mar;12(3):301-11 PMID: 10755617
  10. Constitutive synthesis of tumor necrosis factor in the thymus.
    Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4864-8 PMID: 1594585
  11. The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein.
    J Biol Chem. 1990 Sep 5;265(25):14705-8 PMID: 2118515
  12. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death.
    Science. 1996 Nov 1;274(5288):782-4 PMID: 8864118
  13. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB.
    Science. 1996 Nov 1;274(5288):784-7 PMID: 8864119
  14. Suppression of TNF-alpha-induced apoptosis by NF-kappaB.
    Science. 1996 Nov 1;274(5288):787-9 PMID: 8864120
  15. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappaB activation prevents cell death.
    Cell. 1996 Nov 1;87(3):565-76 PMID: 8898208
  16. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation.
    Science. 1998 Sep 11;281(5383):1680-3 PMID: 9733516
  17. The zinc finger protein A20 inhibits TNF-induced NF-kappaB-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal and directly binds to a novel NF-kappaB-inhibiting protein ABIN.
    J Cell Biol. 1999 Jun 28;145(7):1471-82 PMID: 10385526
  18. A20 zinc finger protein inhibits TNF and IL-1 signaling.
    J Immunol. 1996 Feb 1;156(3):1166-73 PMID: 8557994
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
0036-8075
DOI
10.1126/science.289.5488.2350
Published
2000-09-29
Pages
2350-4
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3582399
Subset
IM
Grants
NIGMS NIH HHS · T32GM07839 · United States
NIDDK NIH HHS · R01 DK052751 · United States
NIAID NIH HHS · R01 AI045860 · United States
NIGMS NIH HHS · T32 GM007839 · United States
NIGMS NIH HHS · T32 GM007183 · United States
NIGMS NIH HHS · 5T32GM07183 · United States
External Links
PubMed source DOI: 10.1126/science.289.5488.2350 PMC Full Text View journal details
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