The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Regulates Tumor Necrosis Factor mRNA Stability and Translation Mainly by Altering Tristetraprolin Expression, Stability, and Binding to Adenine/Uridine-Rich Element
Open accessAbstract
The mitogen-activated protein kinase (MAPK) p38/MAPK-activated protein kinase 2 (MK2) signaling pathway plays an important role in the posttranscriptional regulation of tumor necrosis factor (TNF), which is dependent on the adenine/uridine-rich element (ARE) in the 3' untranslated region of TNF mRNA. After lipopolysaccharide (LPS) stimulation, MK2-deficient macrophages show a 90% reduction in TNF production compared to the wild type. Tristetraprolin (TTP), a protein induced by LPS, binds ARE and destabilizes TNF mRNA. Accordingly, macrophages lacking TTP produce large amounts of TNF. Here, we generated MK2/TTP double knockout mice and show that, after LPS stimulation, bone marrow-derived macrophages produce TNF mRNA and protein levels comparable to those of TTP knockout cells, indicating that in the regulation of TNF biosynthesis TTP is genetically downstream of MK2. In addition, we show that MK2 is essential for the stabilization of TTP mRNA, and phosphorylation by MK2 leads to increased TTP protein stability but reduced ARE affinity. These data suggest that MK2 inhibits the mRNA destabilizing activity of TTP and, in parallel, codegradation of TTP together, with the target mRNA resulting in increased cellular levels of TTP.
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Cites
Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability
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Self-citationMAPKAP kinase 2 is essential for LPS-induced TNF-α biosynthesis
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Self-citationStress granules: sites of mRNA triage that regulate mRNA stability and translatability
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MK2‐induced tristetraprolin:14‐3‐3 complexes prevent stress granule association and ARE‐mRNA decay
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Self-citationThe p38 MAP kinase pathway as a therapeutic target in inflammatory disease
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Schoenberg, D. R., & Maquat, L. E. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3160 · Cited by 656
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Brooks, S. A., & Blackshear, P. J. (2013) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2013.02.003 · Cited by 391
Self-citationmiR‐29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis
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Metadata
- Authors
- Hitti, E., Iakovleva, T., Brook, M., Deppenmeier, S., Gruber, A. D., Radzioch, D., Clark, A. R., Blackshear, P. J., Kotlyarov, A., & Gaestel, M.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2006-03-01
- Volume
- 26
- Issue
- 6
- Pages
- 2399-2407
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2155905959
- Cited by
- 389
- References
- 35
- FWCI
- 13.51
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Regulates Tumor Necrosis Factor mRNA Stability and Translation Mainly by Altering Tristetraprolin Expression, Stability, and Binding to Adenine/Uridine-Rich Element. https://app.cochat.ai/papers/10.1128/mcb.26.6.2399-2407.2006
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- Hitti, E., Iakovleva, T., Brook, M., Deppenmeier, S., Gruber, A. D., Radzioch, D., Clark, A. R., Blackshear, P. J., Kotlyarov, A., & Gaestel, M. (2006). Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Regulates Tumor Necrosis Factor mRNA Stability and Translation Mainly by Altering Tristetraprolin Expression, Stability, and Binding to Adenine/Uridine-Rich Element. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.26.6.2399-2407.2006
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