PMID- 25056949
OWN - NLM
STAT- MEDLINE
DCOM- 20150128
LR  - 20220129
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 289
IP  - 36
DP  - 2014 Sep 5
TI  - Polyubiquitinated tristetraprolin protects from TNF-induced, caspase-mediated 
      apoptosis.
PG  - 25088-100
LID - 10.1074/jbc.M114.563312 [doi]
AB  - Binding of TNF to its receptor (TNFR1) elicits the spatiotemporal assembly of two 
      signaling complexes that coordinate the balance between cell survival and cell 
      death. We have shown previously that, following TNF treatment, the mRNA decay 
      protein tristetraprolin (TTP) is Lys-63-polyubiquitinated by TNF 
      receptor-associated factor 2 (TRAF2), suggesting a regulatory role in TNFR 
      signaling. Here we demonstrate that TTP interacts with TNFR1 in a TRAF2-dependent 
      manner, thereby initiating the MEKK1/MKK4-dependent activation of JNK activities. 
      This regulatory function toward JNK activation but not NF-kappaB activation depends 
      on lysine 105 of TTP, which we identified as the corresponding TRAF2 
      ubiquitination site. Disabling TTP polyubiquitination results in enhanced 
      TNF-induced apoptosis in cervical cancer cells. Together, we uncover a novel 
      aspect of TNFR1 signaling where TTP, in alliance with TRAF2, acts as a balancer 
      of JNK-mediated cell survival versus death.
CI  - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Resch, Ulrike
AU  - Resch U
AD  - From the Department of Vascular Biology and Thrombosis Research, Medical 
      University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.
FAU - Cuapio, Angelica
AU  - Cuapio A
AD  - From the Department of Vascular Biology and Thrombosis Research, Medical 
      University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.
FAU - Sturtzel, Caterina
AU  - Sturtzel C
AD  - From the Department of Vascular Biology and Thrombosis Research, Medical 
      University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.
FAU - Hofer, Erhard
AU  - Hofer E
AD  - From the Department of Vascular Biology and Thrombosis Research, Medical 
      University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.
FAU - de Martin, Rainer
AU  - de Martin R
AD  - From the Department of Vascular Biology and Thrombosis Research, Medical 
      University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.
FAU - Holper-Schichl, Yvonne M
AU  - Holper-Schichl YM
AD  - From the Department of Vascular Biology and Thrombosis Research, Medical 
      University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria 
      yvonne.holper-schichl@meduniwien.ac.at yvonne.schichl@gmx.net.
LA  - eng
GR  - T 511/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140723
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tristetraprolin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 120904-94-1 (Polyubiquitin)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (MAP2K4 protein, human)
RN  - EC 3.4.22.- (Caspases)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Caspases/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Enzyme Activation/drug effects
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Lysine/metabolism
MH  - MAP Kinase Kinase 4/metabolism
MH  - MAP Kinase Kinase Kinase 1/metabolism
MH  - Mice, Knockout
MH  - Mutation
MH  - NF-kappa B/metabolism
MH  - Polyubiquitin/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - TNF Receptor-Associated Factor 2/genetics/metabolism
MH  - Tristetraprolin/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Ubiquitination/drug effects
PMC - PMC4155675
OTO - NOTNLM
OT  - Apoptosis
OT  - Cell Proliferation
OT  - NF-kappaB
OT  - Tristetraprolin
OT  - Tumor Necrosis Factor (TNF)
OT  - c-Jun N-terminal Kinase (JNK)
EDAT- 2014/07/25 06:00
MHDA- 2015/01/30 06:00
PMCR- 2015/09/05
CRDT- 2014/07/25 06:00
PHST- 2014/07/25 06:00 [entrez]
PHST- 2014/07/25 06:00 [pubmed]
PHST- 2015/01/30 06:00 [medline]
PHST- 2015/09/05 00:00 [pmc-release]
AID - S0021-9258(20)31662-8 [pii]
AID - M114.563312 [pii]
AID - 10.1074/jbc.M114.563312 [doi]
PST - ppublish
SO  - J Biol Chem. 2014 Sep 5;289(36):25088-100. doi: 10.1074/jbc.M114.563312. Epub 
      2014 Jul 23.