PMID- 17606294
OWN - NLM
STAT- MEDLINE
DCOM- 20071109
LR  - 20161124
IS  - 0161-5890 (Print)
IS  - 0161-5890 (Linking)
VI  - 45
IP  - 1
DP  - 2008 Jan
TI  - Tristetraprolin regulates TNF TNF-alpha mRNA stability via a proteasome dependent 
      mechanism involving the combined action of the ERK and p38 pathways.
PG  - 13-24
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a central mediator of inflammation. 
      TNF-alpha expression is regulated by transcriptional and post-transcriptional 
      mechanisms, including mRNA stability and translation. Post-transcriptional 
      control operates through cis-elements in the 3' Untranslated-Region of the 
      TNF-alpha mRNA to which trans-acting proteins bind. One of the best characterized 
      trans-acting proteins is Tristetraprolin (TTP), which regulates TNF-alpha message 
      stability. However, the precise mechanisms controlling TNF-alpha message 
      stability are unclear, with data supporting a role for the proteasome, the 
      exosome, and the RNA processing-body (P-body), as well as the involvement of the 
      microRNAs. We examined the effect of proteasome inhibition on endogenous 
      TNF-alpha mRNA stability, TNF-alpha 3'UTR reporter expression and TTP function in 
      the RAW264.7 cells. These data establish that proteasome inhibition stabilized 
      endogenous TNF-alpha mRNA, increased TTP protein levels but inhibited TTP 
      mediated TNF-alpha mRNA decay. Importantly, proteasome inhibition stabilized the 
      TNF-alpha message to the same degree as LPS stimulation. To further characterize 
      the control of TTP function, we examined the combinatorial effect of p38, ERK and 
      JNK activation on TNF-alpha post-transcriptional expression and TTP function. 
      These data establish that TTP mediated TNF-alpha mRNA decay is inhibited by the 
      combined activation of ERK and p38 and not by p38 activation alone. The combined 
      activation of ERK/p38 was sufficient to stabilize endogenous TNF-alpha mRNA to 
      the same degree as LPS stimulation. Together these data indicate that the 
      proteasome is a critical control point for TTP mediated TNF-alpha mRNA decay and 
      activation of both ERK and p38 is required to inhibit TTP function and stabilize 
      TNF-alpha mRNA.
FAU - Deleault, Kristen M
AU  - Deleault KM
AD  - Department of Medicine, Dartmouth Medical School, 1 Medical Center Dr., Lebanon, 
      NH 03756, USA.
FAU - Skinner, Stephen J
AU  - Skinner SJ
FAU - Brooks, Seth A
AU  - Brooks SA
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070702
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Leupeptins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tristetraprolin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Animals
MH  - Cell Line
MH  - Enzyme Activation/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Leupeptins/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Models, Biological
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Proteasome Inhibitors
MH  - Protein Biosynthesis/drug effects
MH  - *RNA Stability/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Transcription, Genetic/drug effects
MH  - Tristetraprolin/*metabolism
MH  - Tumor Necrosis Factor-alpha/biosynthesis/genetics/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2007/07/04 09:00
MHDA- 2007/11/10 09:00
CRDT- 2007/07/04 09:00
PHST- 2007/04/11 00:00 [received]
PHST- 2007/05/16 00:00 [revised]
PHST- 2007/05/17 00:00 [accepted]
PHST- 2007/07/04 09:00 [pubmed]
PHST- 2007/11/10 09:00 [medline]
PHST- 2007/07/04 09:00 [entrez]
AID - S0161-5890(07)00227-1 [pii]
AID - 10.1016/j.molimm.2007.05.017 [doi]
PST - ppublish
SO  - Mol Immunol. 2008 Jan;45(1):13-24. doi: 10.1016/j.molimm.2007.05.017. Epub 2007 
      Jul 2.