PMID- 16936264
OWN - NLM
STAT- MEDLINE
DCOM- 20061024
LR  - 20190608
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 169
IP  - 3
DP  - 2006 Sep
TI  - JAB1 determines the response of rheumatoid arthritis synovial fibroblasts to 
      tumor necrosis factor-alpha.
PG  - 889-902
AB  - Fibroblast-like synoviocytes (FLSs) of patients with rheumatoid arthritis (RA 
      FLSs) exhibit prosurvival, rather than apoptotic, response to tumor necrosis 
      factor (TNF)-alpha stimulation. Here, we show that JAB1 is a critical regulator 
      of the TNF-alpha-mediated anti-apo-ptosis pathways in RA FLSs. We found that 
      knockdown of JAB1 using small interfering (si)RNA led to restoration of the 
      TNF-alpha-induced apoptosis response, reduction of nuclear factor-kappaB 
      activity, delayed degradation of IkappaB-alpha, and inhibited phosphorylation of 
      JNK. Analysis of the interactions of JAB1 by reciprocal co-immunoprecipitations 
      and confocal microscopy revealed that JAB1 interacts with TNF 
      receptor-associated-factor 2 (TRAF2). The generation of the anti-apoptotic signal 
      on binding of TNF-alpha to the TNF receptor (TNFR)1 has been shown to be 
      associated with the recruitment of TRAF2 to the TNFR1 in a process that requires 
      ubiquitination of TRAF2 with lysine-63-linked polyubiquitin chains. We found that 
      TNF-alpha stimulation of JAB1 siRNA-transfected RA FLSs failed to stimulate 
      ubiquitination of TRAF2. Thus, we conclude that JAB1-regulated ubiquitination of 
      TRAF2 is a novel mechanism whereby TNF-alpha can induce anti-apoptosis signaling 
      and production of matrix metalloproteinases through activation of nuclear 
      factor-kappaB and JNK in RA FLSs.
FAU - Wang, Jianhua
AU  - Wang J
AD  - Department of Medicine, Division of Clinical Immunology and Rheumatology, 
      University of Alabama at Birmingham 35294-0007, USA.
FAU - Li, Chuanyu
AU  - Li C
FAU - Liu, Yuelong
AU  - Liu Y
FAU - Mei, Wan
AU  - Mei W
FAU - Yu, Shaohua
AU  - Yu S
FAU - Liu, Cunren
AU  - Liu C
FAU - Zhang, Liming
AU  - Zhang L
FAU - Cao, Xu
AU  - Cao X
FAU - Kimberly, Robert P
AU  - Kimberly RP
FAU - Grizzle, William
AU  - Grizzle W
FAU - Zhang, Huang-Ge
AU  - Zhang HG
LA  - eng
GR  - P P30 AR48311/AR/NIAMS NIH HHS/United States
GR  - P30 AR048311/AR/NIAMS NIH HHS/United States
GR  - R01 CA107181/CA/NCI NIH HHS/United States
GR  - R01 CA116092/CA/NCI NIH HHS/United States
GR  - R21 AR43321/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Ubiquitin)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.-.- (COPS5 protein, human)
RN  - EC 3.4.19.12 (COP9 Signalosome Complex)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - *Apoptosis/drug effects
MH  - Arthritis, Rheumatoid/*metabolism/pathology
MH  - COP9 Signalosome Complex
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Fibroblasts/*metabolism/pathology
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/antagonists & 
      inhibitors/*metabolism
MH  - MAP Kinase Kinase 4/metabolism
MH  - Matrix Metalloproteinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Peptide Hydrolases/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Processing, Post-Translational/drug effects
MH  - RNA, Small Interfering/pharmacology
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Signal Transduction/drug effects
MH  - Synovial Fluid/metabolism
MH  - Synovial Membrane/*metabolism/pathology
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
MH  - Ubiquitin/metabolism
PMC - PMC1698810
EDAT- 2006/08/29 09:00
MHDA- 2006/10/25 09:00
PMCR- 2007/03/01
CRDT- 2006/08/29 09:00
PHST- 2006/08/29 09:00 [pubmed]
PHST- 2006/10/25 09:00 [medline]
PHST- 2006/08/29 09:00 [entrez]
PHST- 2007/03/01 00:00 [pmc-release]
AID - S0002-9440(10)62766-6 [pii]
AID - 10.2353/ajpath.2006.051161 [doi]
PST - ppublish
SO  - Am J Pathol. 2006 Sep;169(3):889-902. doi: 10.2353/ajpath.2006.051161.