PMID- 10385526
OWN - NLM
STAT- MEDLINE
DCOM- 19990802
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 145
IP  - 7
DP  - 1999 Jun 28
TI  - 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.
PG  - 1471-82
AB  - The zinc finger protein A20 is a tumor necrosis factor (TNF)- and interleukin 1
      (IL-1)-inducible protein that negatively regulates nuclear factor-kappa B
      (NF-kappaB)-dependent gene expression. However, the molecular mechanism by which 
      A20 exerts this effect is still unclear. We show that A20 does not inhibit TNF-
      induced nuclear translocation and DNA binding of NF-kappaB, although it
      completely prevents the TNF- induced activation of an NF-kappaB-dependent
      reporter gene, as well as TNF-induced IL-6 and granulocyte macrophage-colony
      stimulating factor gene expression. Moreover, NF-kappaB activation induced by
      overexpression of the TNF receptor-associated proteins TNF receptor-associated
      death domain protein (TRADD), receptor interacting protein (RIP), and TNF recep- 
      tor-associated factor 2 (TRAF2) was also inhibited by expression of A20, whereas 
      NF-kappaB activation induced by overexpression of NF-kappaB-inducing kinase (NIK)
      or the human T cell leukemia virus type 1 (HTLV-1) Tax was unaffected. These
      results demonstrate that A20 inhibits NF-kappaB-dependent gene expression by
      interfering with a novel TNF-induced and RIP- or TRAF2-mediated pathway that is
      different from the NIK-IkappaB kinase pathway and that is specifically involved
      in the transactivation of NF-kappaB. Via yeast two-hybrid screening, we found
      that A20 binds to a novel protein, ABIN, which mimics the NF-kappaB inhibiting
      effects of A20 upon overexpression, suggesting that the effect of A20 is mediated
      by its interaction with this NF-kappaB inhibiting protein, ABIN.
FAU - Heyninck, K
AU  - Heyninck K
AD  - Department of Molecular Biology, Flanders Interuniversity Institute for
      Biotechnology, University of Ghent, B-9000 Ghent, Belgium.
FAU - De Valck, D
AU  - De Valck D
FAU - Vanden Berghe, W
AU  - Vanden Berghe W
FAU - Van Criekinge, W
AU  - Van Criekinge W
FAU - Contreras, R
AU  - Contreras R
FAU - Fiers, W
AU  - Fiers W
FAU - Haegeman, G
AU  - Haegeman G
FAU - Beyaert, R
AU  - Beyaert R
LA  - eng
SI  - GENBANK/AJ242777
SI  - GENBANK/AJ242778
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Gene Products, tax)
RN  - 0 (Interleukin-6)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - 0 (TNF Receptor-Associated Death Domain Protein)
RN  - 0 (TNF Receptor-Associated Factor 1)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tradd protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Tumor Necrosis Factor Receptor-Associated Peptides and Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (RIPK1 protein, human)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ripk1 protein, mouse)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (NF-kappa B kinase)
RN  - EC 3.4.19.12 (TNFAIP3 protein, human)
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.22.- (Tnfaip3 protein, mouse)
SB  - IM
SB  - X
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cysteine Endopeptidases
MH  - DNA/genetics/metabolism
MH  - DNA-Binding Proteins
MH  - Enzyme Activation/drug effects
MH  - Gene Products, tax/genetics/metabolism
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/genetics
MH  - Humans
MH  - Interleukin-6/genetics
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Nuclear Proteins/genetics/physiology
MH  - Protein Binding/drug effects
MH  - Protein-Serine-Threonine Kinases/genetics/metabolism
MH  - Proteins/chemistry/genetics/*metabolism
MH  - Receptor-Interacting Protein Serine-Threonine Kinases
MH  - Signal Transduction/drug effects
MH  - TNF Receptor-Associated Death Domain Protein
MH  - TNF Receptor-Associated Factor 1
MH  - TNF Receptor-Associated Factor 2
MH  - Trans-Activators/genetics/physiology
MH  - *Transcriptional Activation/drug effects
MH  - *Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
MH  - Tumor Necrosis Factor alpha-Induced Protein 3
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/pharmacology
MH  - Yeasts/genetics
MH  - Zinc Fingers
MH  - p38 Mitogen-Activated Protein Kinases
PMC - PMC2133159
EDAT- 1999/06/29 00:00
MHDA- 1999/06/29 00:01
CRDT- 1999/06/29 00:00
PHST- 1999/06/29 00:00 [pubmed]
PHST- 1999/06/29 00:01 [medline]
PHST- 1999/06/29 00:00 [entrez]
AID - 10.1083/jcb.145.7.1471 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Jun 28;145(7):1471-82. doi: 10.1083/jcb.145.7.1471.