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| Subject Categories: Signal Transduction | RNA |
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| The EMBO Journal
(2004) 23, 1313–1324, doi:10.1038/sj.emboj.7600163 Published online 11 March 2004 |
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| MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay |
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| Georg Stoecklin1, Tiffany Stubbs1, Nancy Kedersha1, Stephen Wax1, William FC Rigby2, T Keith Blackwell3 and Paul Anderson1 |
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1 Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA 2 Department of Medicine, Dartmouth Medical School, Lebanon, NH, USA 3 CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA, USA To whom correspondence should be addressed Paul Anderson, Division of Rheumatology and Immunology, Brigham and Women's Hospital, Smith 652, One Jimmy Fund Way, Boston, MA 02115, USA. Tel.: +1 617 525 1202; Fax: +1 617 525 1310; E-mail: panderson@rics.bwh.harvard.edu Received 1 October 2003; Accepted 16 February 2004; Published online 11 March 2004. |
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| Abstract |
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Stress granules (SGs) are dynamic cytoplasmic foci at which stalled translation initiation complexes accumulate in cells subjected to environmental stress. SG-associated proteins such as TIA-1, TIAR and HuR bind to AU-rich element (ARE)-containing mRNAs and control their translation and stability. Here we show that tristetraprolin (TTP), an ARE-binding protein that destabilizes ARE-mRNAs, is recruited to SGs that are assembled in response to FCCP-induced energy deprivation, but not arsenite-induced oxidative stress. Exclusion of TTP from arsenite-induced SGs is a consequence of MAPKAP kinase-2 (MK2)-induced phosphorylation at serines 52 and 178, which promotes the assembly of TTP:14-3-3 complexes. 14-3-3 binding excludes TTP from SGs and inhibits TTP-dependent degradation of ARE-containing transcripts. In activated RAW 264.7 macrophages, endogenous TTP:14-3-3 complexes bind to ARE-RNA. Our data reveal the mechanism by which the p38-MAPK/MK2 kinase cascade inhibits TTP-mediated degradation of ARE-containing transcripts and thereby contributes to lipopolysaccharide-induced TNF expression. |
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| Keywords: AU-rich element, MAPKAP kinase-2, mRNA turnover, TNF, TTP |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B The EMBO Journal Article (08 Dec 2004) Oncogene Original Article Functional cloning of BRF1, a regulator of ARE-dependent mRNA turnover The EMBO Journal Article (02 Sep 2002) Targeting mRNA Stability Arrests Inflammatory Bone Loss Molecular Therapy Original Article |
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