PMID- 24008839
OWN - NLM
STAT- MEDLINE
DCOM- 20140214
LR  - 20220330
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 3
DP  - 2013
TI  - Involvement of A20 in the molecular switch that activates the non-canonical NF-small ka, CyrillicB 
      pathway.
PG  - 2568
LID - 10.1038/srep02568 [doi]
LID - 2568
AB  - The non-canonical NF-kappaB pathway is crucial for the immune system. A critical 
      event in activation of the non-canonical pathway is the attenuation of 
      NF-kappaB-inducing kinase (NIK) degradation, which is promoted by continuous 
      polyubiquitination of NIK catalyzed by the NIK ubiquitin-ligase complex composed 
      of cellular inhibitor of apoptosis protein 1 and 2 (cIAP1/2), TNF 
      receptor-associated factor 2 (TRAF2), and TRAF3. However, the molecular mechanism 
      of stimulation-dependent NIK stabilization remains poorly understood. Here, we 
      show that A20, a ubiquitin-editing enzyme, promotes efficient activation of the 
      non-canonical pathway independent of its catalytic activity. A20 directly binds 
      to cIAP1 through the seventh zinc finger of A20, resulting in dissociation of the 
      TRAF2/TRAF3 interaction, thereby inactivating the ligase complex to stabilize 
      NIK. Given that A20 negatively regulates the canonical pathway, A20 is likely 
      involved in the molecular switch that promotes the transition from canonical to 
      non-canonical activation for proper control of the immune system.
FAU - Yamaguchi, Noritaka
AU  - Yamaguchi N
AD  - Division of Cellular and Molecular Biology, Department of Cancer Biology, 
      Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, 
      Tokyo, Japan.
FAU - Oyama, Masaaki
AU  - Oyama M
FAU - Kozuka-Hata, Hiroko
AU  - Kozuka-Hata H
FAU - Inoue, Jun-ichiro
AU  - Inoue J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (TNF Receptor-Associated Factor 3)
RN  - 0 (Ubiquitins)
RN  - EC 3.4.19.12 (TNFAIP3 protein, human)
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
SB  - IM
MH  - DNA-Binding Proteins/*metabolism
MH  - Inhibitor of Apoptosis Proteins/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Signal Transduction/physiology
MH  - TNF Receptor-Associated Factor 2/*metabolism
MH  - TNF Receptor-Associated Factor 3/*metabolism
MH  - Tumor Necrosis Factor alpha-Induced Protein 3
MH  - Ubiquitination/*physiology
MH  - Ubiquitins/*metabolism
PMC - PMC3764444
EDAT- 2013/09/07 06:00
MHDA- 2014/02/15 06:00
PMCR- 2013/09/06
CRDT- 2013/09/07 06:00
PHST- 2013/01/18 00:00 [received]
PHST- 2013/08/19 00:00 [accepted]
PHST- 2013/09/07 06:00 [entrez]
PHST- 2013/09/07 06:00 [pubmed]
PHST- 2014/02/15 06:00 [medline]
PHST- 2013/09/06 00:00 [pmc-release]
AID - srep02568 [pii]
AID - 10.1038/srep02568 [doi]
PST - ppublish
SO  - Sci Rep. 2013;3:2568. doi: 10.1038/srep02568.