PMID- 15572357
OWN - NLM
STAT- MEDLINE
DCOM- 20050418
LR  - 20220321
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 7
DP  - 2005 Feb 18
TI  - The Met-196 -> Arg variation of human tumor necrosis factor receptor 2 (TNFR2) 
      affects TNF-alpha-induced apoptosis by impaired NF-kappaB signaling and target 
      gene expression.
PG  - 5994-6004
AB  - Tumor necrosis factor-alpha (TNF-alpha)-induced signaling is pivotally involved 
      in the pathogenesis of chronic inflammatory diseases. A polymorphism in the TNF 
      receptor 2 (TNFR2) gene resulting in a juxtamembrane inversion from methionine 
      (TNFR2(196MET)) to arginine (TNFR2(196ARG)) has been genetically associated with 
      an increased risk for systemic lupus erythematosus and familial rheumatoid 
      arthritis. Albeit the mutation does not affect the TNF binding kinetics of TNFR2, 
      the present study provides evidence that the mutation results in a significantly 
      lower capability to induce TNFR2-mediated NF-kappaB activation. Pretriggering of 
      TNFR2 with a receptor-specific mutein leads to an enhancement of TNFR1-induced 
      apoptosis, which is further increased in cells carrying the TNFR2(196ARG) 
      variant. A diminished induction of NF-kappaB-dependent target genes conveying 
      either anti-apoptotic or pro-inflammatory functions, such as cIAP1, TRAF1, IL-6, 
      or IL-8 is observed. The mutated form TNFR2(196ARG) shows a reduction of 
      inducible TRAF2 recruitment upon TNF-alpha stimulation. The findings suggest a 
      common molecular mechanism for the involvement of the TNFR2(196ARG) variant in 
      the etiopathogenesis of different chronic inflammatory disorders.
FAU - Till, Andreas
AU  - Till A
AD  - Institute of Clinical Molecular Biology at the Christian-Albrechts-University 
      Kiel, Schittenhelmstrasse 12, 24105 Kiel, Germany.
FAU - Rosenstiel, Philip
AU  - Rosenstiel P
FAU - Krippner-Heidenreich, Anja
AU  - Krippner-Heidenreich A
FAU - Mascheretti-Croucher, Silvia
AU  - Mascheretti-Croucher S
FAU - Croucher, Peter J P
AU  - Croucher PJ
FAU - Schafer, Heiner
AU  - Schafer H
FAU - Scheurich, Peter
AU  - Scheurich P
FAU - Seegert, Dirk
AU  - Seegert D
FAU - Schreiber, Stefan
AU  - Schreiber S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041130
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 94ZLA3W45F (Arginine)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Arginine/*genetics/metabolism
MH  - Cytokines/metabolism
MH  - Fibroblasts
MH  - Gene Expression Regulation/*drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Immunoprecipitation
MH  - Interleukin-6/analysis/metabolism
MH  - Interleukin-8/analysis/metabolism
MH  - Methionine/*genetics/metabolism
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Mutation/genetics
MH  - NF-kappa B/*metabolism
MH  - Receptors, Tumor Necrosis Factor, Type II/chemistry/genetics/*metabolism
MH  - Signal Transduction/drug effects
MH  - Solubility
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2004/12/02 09:00
MHDA- 2005/04/19 09:00
CRDT- 2004/12/02 09:00
PHST- 2004/12/02 09:00 [pubmed]
PHST- 2005/04/19 09:00 [medline]
PHST- 2004/12/02 09:00 [entrez]
AID - S0021-9258(19)63107-8 [pii]
AID - 10.1074/jbc.M411541200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Feb 18;280(7):5994-6004. doi: 10.1074/jbc.M411541200. Epub 2004 
      Nov 30.