PMID- 21921033
OWN - NLM
STAT- MEDLINE
DCOM- 20120109
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 44
DP  - 2011 Nov 4
TI  - Novel phosphorylation-dependent ubiquitination of tristetraprolin by 
      mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 
      kinase 1 (MEKK1) and tumor necrosis factor receptor-associated factor 2 (TRAF2).
PG  - 38466-38477
LID - S0021-9258(20)50691-1 [pii]
LID - 10.1074/jbc.M111.254888 [doi]
AB  - Acute versus chronic inflammation is controlled by the accurate activation and 
      regulation of interdependent signaling cascades. TNF-receptor 1 engagement 
      concomitantly activates NF-kappaB and JNK signaling. The correctly timed activation 
      of these pathways is the key to account for the balance between NF-kappaB-mediated 
      cell survival and cell death, the latter fostered by prolonged JNK activation. 
      Tristetraprolin (TTP), initially described as an mRNA destabilizing protein, acts 
      as negative feedback regulator of the inflammatory response: it destabilizes 
      cytokine-mRNAs but also acts as an NF-kappaB inhibitor by interfering with the 
      p65/RelA nuclear import pathway. Our biochemical studies provide evidence that 
      TTP contributes to the NF-kappaB/JNK balance. We find that the MAP 3-kinase MEKK1 
      acts as a novel TTP kinase that, together with the TNF receptor-associated factor 
      2 (TRAF2), constitutes not only a main determinate of the NF-kappaB-JNK cross-talk 
      but also facilitates "TTP hypermodification": MEKK1 triggers TTP phosphorylation 
      as prerequisite for its Lys-63-linked, TRAF2-mediated ubiquitination. 
      Consequently, TTP no longer affects NF-kappaB activity but promotes the activation of 
      JNK. Based on our data, we suggest a model where upon TNFalpha induction, TTP 
      transits a hypo- to hypermodified state, thereby contributing to the molecular 
      regulation of NF-kappaB versus JNK signaling cascades.
FAU - Schichl, Yvonne M
AU  - Schichl YM
AD  - Department of Vascular Biology and Thrombosis Research, Center for Physiology and 
      Pharmacology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, 
      Austria. Electronic address: yvonne.schichl@gmx.net.
FAU - Resch, Ulrike
AU  - Resch U
AD  - Department of Vascular Biology and Thrombosis Research, Center for Physiology and 
      Pharmacology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, 
      Austria.
FAU - Lemberger, Christof E
AU  - Lemberger CE
AD  - Department of Vascular Biology and Thrombosis Research, Center for Physiology and 
      Pharmacology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, 
      Austria.
FAU - Stichlberger, Dominik
AU  - Stichlberger D
AD  - Department of Vascular Biology and Thrombosis Research, Center for Physiology and 
      Pharmacology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, 
      Austria.
FAU - de Martin, Rainer
AU  - de Martin R
AD  - Department of Vascular Biology and Thrombosis Research, Center for Physiology and 
      Pharmacology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, 
      Austria.
LA  - eng
GR  - T 511/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110915
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 (Ubiquitin)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP3K1 protein, human)
SB  - IM
MH  - Adenoviridae/metabolism
MH  - Cell Survival
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - I-kappa B Kinase/metabolism
MH  - Inflammation
MH  - MAP Kinase Kinase Kinase 1/*metabolism
MH  - MAP Kinase Signaling System
MH  - Mutation
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - Receptors, Tumor Necrosis Factor, Type I/chemistry
MH  - Signal Transduction
MH  - TNF Receptor-Associated Factor 2/*metabolism
MH  - Tristetraprolin/*chemistry
MH  - Ubiquitin/*chemistry
PMC - PMC3207473
EDAT- 2011/09/17 06:00
MHDA- 2012/01/10 06:00
PMCR- 2012/11/04
CRDT- 2011/09/17 06:00
PHST- 2011/09/17 06:00 [entrez]
PHST- 2011/09/17 06:00 [pubmed]
PHST- 2012/01/10 06:00 [medline]
PHST- 2012/11/04 00:00 [pmc-release]
AID - S0021-9258(20)50691-1 [pii]
AID - M111.254888 [pii]
AID - 10.1074/jbc.M111.254888 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Nov 4;286(44):38466-38477. doi: 10.1074/jbc.M111.254888. Epub 
      2011 Sep 15.