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.
Original language | English (US) |
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Pages (from-to) | 453-462 |
Number of pages | 10 |
Journal | Biological Chemistry |
Volume | 390 |
Issue number | 5-6 |
DOIs | |
State | Published - May 1 2009 |
Keywords
- Apoptosis
- DsRNA
- Protein translation
- Ribosome
- Ribotoxic stress
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Clinical Biochemistry