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Cited by 393

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MK2 Targets AU-rich Elements and Regulates Biosynthesis of Tumor Necrosis Factor and Interleukin-6 Independently at Different Post-transcriptional Levels

Open access
Neininger, Armin, Kontoyiannis, Dimitris, Kotlyarov, Alexey, Winzen, Reinhard, Eckert, Rolf, Volk, Hans-Dieter, Holtmann, Helmut, Kollias, George, Gaestel, Matthias·2002·Journal of Biological Chemistry

Abstract

We demonstrate that lipopolysaccharide-induced tumor necrosis factor (TNF) biosynthesis becomes independent of MAPKAP kinase 2 (MK2) when the AU-rich element (ARE) of the TNF gene is deleted. In spleen cells and macrophages where TNF biosynthesis is restored as a result of this deletion, interleukin (IL)-6 biosynthesis is still dependent on MK2. In MK2-deficient macrophages the half-life of IL-6 mRNA is reduced more than 10-fold, whereas the half-life of TNF mRNA is only weakly decreased. It is shown that the stability of a reporter mRNA carrying the AU-rich 3'-untranslated region (3'-UTR) of IL-6 is increased by MK2. The data provide in vivo evidence that the AU-rich 3'-UTRs of TNF and IL-6 are downstream to MK2 signaling and make MK2 an essential component of mechanisms that regulate biosynthesis of IL-6 at the levels of mRNA stability, and of TNF mainly through TNF-ARE-dependent translational control.

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Metadata

Authors
Neininger, A., Kontoyiannis, D., Kotlyarov, A., Winzen, R., Eckert, R., Volk, H.-D., Holtmann, H., Kollias, G., & Gaestel, M.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-02
Volume
277
Issue
5
Pages
3065-3068
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2039077632
Cited by
393
References
2
FWCI
7.99
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: MK2 Targets AU-rich Elements and Regulates Biosynthesis of Tumor Necrosis Factor and Interleukin-6 Independently at Different Post-transcriptional Levels. https://app.cochat.ai/papers/10.1074/jbc.c100685200
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Neininger, A., Kontoyiannis, D., Kotlyarov, A., Winzen, R., Eckert, R., Volk, H.-D., Holtmann, H., Kollias, G., & Gaestel, M. (2002). MK2 Targets AU-rich Elements and Regulates Biosynthesis of Tumor Necrosis Factor and Interleukin-6 Independently at Different Post-transcriptional Levels. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.c100685200

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