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Posttranscriptional regulation of TNFalpha expression via eukaryotic initiation factor 4E (eIF4E) phosphorylation in mouse macrophages.

Andersson, Karolina LU and Sundler, Roger LU (2006) In Cytokine 33(1). p.52-57
Abstract
Resident mouse macrophages secrete Tumor necrosis factor α (TNFα) upon challenge with LPS. The production of TNFα is controlled not only at the transcription of the gene, but also by strong posttranscriptional regulation. When macrophages are stimulated with LPS different signal transduction pathways become activated. Here we show that the combination of the 2 kinases p38 and MEK and presumably ERK1/2 regulate translation of TNFα, through the downstream kinase Mnk1. TNFα production is inhibited in a concentration-dependent manner by CGP57380 (Mnk1 inhibitor). The corresponding mRNA results show that the inhibition targets posttranscriptional regulation and is paralleled by inhibition of the phosphorylation of eukaryotic initiation factor... (More)
Resident mouse macrophages secrete Tumor necrosis factor α (TNFα) upon challenge with LPS. The production of TNFα is controlled not only at the transcription of the gene, but also by strong posttranscriptional regulation. When macrophages are stimulated with LPS different signal transduction pathways become activated. Here we show that the combination of the 2 kinases p38 and MEK and presumably ERK1/2 regulate translation of TNFα, through the downstream kinase Mnk1. TNFα production is inhibited in a concentration-dependent manner by CGP57380 (Mnk1 inhibitor). The corresponding mRNA results show that the inhibition targets posttranscriptional regulation and is paralleled by inhibition of the phosphorylation of eukaryotic initiation factor 4E (eIF4E). Unexpectedly, the activation/inhibition of MAPKAP kinase-2 (MK2) does not parallel TNFα production, arguing against a direct/immediate role for this kinase. On the basis of the present and previous results we propose that ARE-containing TNFα mRNA requires phosphorylation of eIF4E for initiation of translation. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CGP57380, Mnk, mRNA translation, SB203580, U0126
in
Cytokine
volume
33
issue
1
pages
52 - 57
publisher
Academic Press
external identifiers
  • pmid:16431125
  • wos:000235735000008
  • scopus:32344445358
ISSN
1096-0023
DOI
10.1016/j.cyto.2005.11.017
language
English
LU publication?
yes
id
da688eb9-ef6c-4a51-b407-4a5ed96e6f3c (old id 150176)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16431125&dopt=Abstract
date added to LUP
2016-04-01 15:34:54
date last changed
2021-10-10 04:40:28
@article{da688eb9-ef6c-4a51-b407-4a5ed96e6f3c,
  abstract     = {Resident mouse macrophages secrete Tumor necrosis factor α (TNFα) upon challenge with LPS. The production of TNFα is controlled not only at the transcription of the gene, but also by strong posttranscriptional regulation. When macrophages are stimulated with LPS different signal transduction pathways become activated. Here we show that the combination of the 2 kinases p38 and MEK and presumably ERK1/2 regulate translation of TNFα, through the downstream kinase Mnk1. TNFα production is inhibited in a concentration-dependent manner by CGP57380 (Mnk1 inhibitor). The corresponding mRNA results show that the inhibition targets posttranscriptional regulation and is paralleled by inhibition of the phosphorylation of eukaryotic initiation factor 4E (eIF4E). Unexpectedly, the activation/inhibition of MAPKAP kinase-2 (MK2) does not parallel TNFα production, arguing against a direct/immediate role for this kinase. On the basis of the present and previous results we propose that ARE-containing TNFα mRNA requires phosphorylation of eIF4E for initiation of translation.},
  author       = {Andersson, Karolina and Sundler, Roger},
  issn         = {1096-0023},
  language     = {eng},
  number       = {1},
  pages        = {52--57},
  publisher    = {Academic Press},
  series       = {Cytokine},
  title        = {Posttranscriptional regulation of TNFalpha expression via eukaryotic initiation factor 4E (eIF4E) phosphorylation in mouse macrophages.},
  url          = {http://dx.doi.org/10.1016/j.cyto.2005.11.017},
  doi          = {10.1016/j.cyto.2005.11.017},
  volume       = {33},
  year         = {2006},
}