PMID- 26224629
OWN - NLM
STAT- MEDLINE
DCOM- 20160201
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 290
IP  - 36
DP  - 2015 Sep 4
TI  - CYLD and the NEMO Zinc Finger Regulate Tumor Necrosis Factor Signaling and Early 
      Embryogenesis.
PG  - 22076-84
LID - 10.1074/jbc.M115.658096 [doi]
AB  - NF-kappaB essential modulator (NEMO) and cylindromatosis protein (CYLD) are 
      intracellular proteins that regulate the NF-kappaB signaling pathway. Although mice 
      with either CYLD deficiency or an alteration in the zinc finger domain of NEMO 
      (K392R) are born healthy, we found that the combination of these two gene defects 
      in double mutant (DM) mice is early embryonic lethal but can be rescued by the 
      absence of TNF receptor 1 (TNFR1). Notably, NEMO was not recruited into the TNFR1 
      complex of DM cells, and consequently NF-kappaB induction by TNF was severely 
      impaired and DM cells were sensitized to TNF-induced cell death. Interestingly, 
      the TNF signaling defects can be fully rescued by reconstitution of DM cells with 
      CYLD lacking ubiquitin hydrolase activity but not with CYLD mutated in TNF 
      receptor-associated factor 2 (TRAF2) or NEMO binding sites. Therefore, our data 
      demonstrate an unexpected non-catalytic function for CYLD as an adapter protein 
      between TRAF2 and the NEMO zinc finger that is important for TNF-induced NF-kappaB 
      signaling during embryogenesis.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Zhao, Yongge
AU  - Zhao Y
AD  - From the Laboratory of Host Defenses, NIAID, National Institutes of Health, 
      Bethesda, Maryland 20892, yongge.zhao@nih.gov.
FAU - Ma, Chi A
AU  - Ma CA
AD  - From the Laboratory of Host Defenses, NIAID, National Institutes of Health, 
      Bethesda, Maryland 20892.
FAU - Wu, Liming
AU  - Wu L
AD  - From the Laboratory of Host Defenses, NIAID, National Institutes of Health, 
      Bethesda, Maryland 20892.
FAU - Iwai, Kazuhiro
AU  - Iwai K
AD  - the Department of Molecular and Cellular Physiology, Graduate School of Medicine, 
      Kyoto University, Kyoto, 606-8501, Japan.
FAU - Ashwell, Jonathan D
AU  - Ashwell JD
AD  - the Laboratory of Immune Cell Biology, NCI, National Institutes of Health, 
      Bethesda, Maryland 20892.
FAU - Oltz, Eugene M
AU  - Oltz EM
AD  - the Department of Pathology and Immunology, Washington University School of 
      Medicine, St. Louis, Missouri 63110, and.
FAU - Ballard, Dean W
AU  - Ballard DW
AD  - the Department of Pathology, Microbiology and Immunology, Vanderbilt University, 
      Nashville, Tennessee 37232.
FAU - Jain, Ashish
AU  - Jain A
AD  - From the Laboratory of Host Defenses, NIAID, National Institutes of Health, 
      Bethesda, Maryland 20892, ashish.jain1@merck.com.
LA  - eng
GR  - R01 AI052379/AI/NIAID NIH HHS/United States
GR  - AI052379/AI/NIAID NIH HHS/United States
GR  - Intramural NIH HHS/United States
GR  - CA082556/CA/NCI NIH HHS/United States
GR  - R01 CA082556/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20150729
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NEMO protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (cylindromatosis protein, mouse)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/genetics
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Embryo, Mammalian/cytology
MH  - Embryonic Development/*genetics
MH  - Fibroblasts/cytology/drug effects/metabolism
MH  - Intracellular Signaling Peptides and Proteins/*genetics/metabolism
MH  - Mice, Knockout
MH  - NF-kappa B/genetics/metabolism
MH  - Protein Binding
MH  - Receptors, Tumor Necrosis Factor, Type I/*genetics/metabolism
MH  - Signal Transduction/drug effects/genetics
MH  - TNF Receptor-Associated Factor 2/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Tumor Suppressor Proteins/*genetics/metabolism
MH  - Zinc Fingers/genetics
PMC - PMC4571959
OTO - NOTNLM
OT  - CYLD
OT  - NEMO
OT  - NF-kappaB (NF-KB)
OT  - cell signaling
OT  - immunodeficiency
OT  - protein complex
OT  - tumor necrosis factor (TNF)
EDAT- 2015/08/01 06:00
MHDA- 2016/02/02 06:00
PMCR- 2016/09/04
CRDT- 2015/07/31 06:00
PHST- 2015/04/16 00:00 [received]
PHST- 2015/07/31 06:00 [entrez]
PHST- 2015/08/01 06:00 [pubmed]
PHST- 2016/02/02 06:00 [medline]
PHST- 2016/09/04 00:00 [pmc-release]
AID - S0021-9258(20)44867-7 [pii]
AID - M115.658096 [pii]
AID - 10.1074/jbc.M115.658096 [doi]
PST - ppublish
SO  - J Biol Chem. 2015 Sep 4;290(36):22076-84. doi: 10.1074/jbc.M115.658096. Epub 2015 
      Jul 29.