Short double-stranded RNAs of specific sequence activate ribosomal TAK1-D and induce a global inhibition of translation
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Abstract
We have previously shown that short double-stranded RNAs of specific sequence induce phosphorylation in the activation loop of splicing variant D of the transforming growth factor β-activated protein kinase 1 (TAK1-D). Here, we further characterize this novel function of TAK1-D and the mechanisms of this dsRNA-triggered phenomenon. Using a dominant negative TAK1-D mutant we demonstrate that TAK1-D activation is functionally required to trigger the activation of p38 MAP kinase and c-JUN terminal kinase and to induce cell death in NCI-H460 cells. While total TAK1-D protein was found in the cytoplasm as well as in the ribosomal fraction, activated TAK1-D phosphorylated on T184 and T187 in the activation loop was found to be exclusively associated with the 80S ribosome. The association of TAK1-D with the ribosome suggests an involvement in translation-dependent signaling and we demonstrate here that dsRNA-mediated activation of TAK1-D leads to a downregulation of mRNA translation. In addition, we show that TAK1-D is also phosphorylated after the induction of ribotoxic stress. Our data indicate that TAK1-D plays a role in the signaling events triggered by selected types of ribotoxic stress.
©2009 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Reviews
- The liaison between apoptotic cells and macrophages – the end programs the beginning
- Activation mechanisms of coagulation factor IX
- Subsite cooperativity in protease specificity
- Minireview
- Retrodifferentiation – a mechanism for cellular regeneration?
- Protein Structure and Function
- The solution structure of pGolemi, a high affinity Mena EVH1 binding miniature protein, suggests explanations for paralog-specific binding to Ena/VASP homology (EVH) 1 domains
- 3D structure of a binary ROP-PRONE complex: the final intermediate for a complete set of molecular snapshots of the RopGEF reaction
- Identification and characterization of a bioactive lantibiotic produced by Staphylococcus warneri
- Role of the polypeptide backbone and post-translational modifications in cross-reactivity of Art v 1, the major mugwort pollen allergen
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- Krüppel-like factor 4 represses transcription of the survivin gene in esophageal cancer cell lines
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- Release of endo-lysosomal cathepsins B, D, and L from IEC6 cells in a cell culture model mimicking intestinal manipulation
- Cathepsin B release from rodent intestine mucosa due to mechanical injury results in extracellular matrix damage in early post-traumatic phases
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- Novel Techniques
- The influenza A virus matrix protein as a marker to monitor initial virus internalisation
- Erratum
- Murine and human cathepsin B exhibit similar properties: possible implications for drug discovery
