Sequence-specific activation of TAK1-D by short double-stranded RNAs induces apoptosis in NCI-H460 cells

Reinhard Kodym, Elisabeth Kodym, Micheal D. Story

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Short double-stranded RNAs (dsRNA) are potent biological entities triggering a number of cellular effects. Most prominent among these is the post-transcriptional gene silencing of target genes by small interfering RNAs (siRNAs). In addition dsRNAs activate signal transduction processes through molecules like PKR or the Toll-like receptor important in viral defense and in explaining off target effects of siRNAs. Only a few of these dsRNA triggered pathways have been characterized yet. Here we show that the splicing variant D of the TAK1 gene is activated by short double-stranded RNAs in a sequence-specific manner. Activation of TAK1-D leads to the downstream activation of the p38 MAPK and of SAPK/JNK but not the NFκB pathway. In the human lung cancer cell line NCI-H460 the activation of these pathways leads to cell cycle arrest and apoptosis. Our results demonstrate that TAK1-D is activated by siRNAs of specific sequences, offering a new explanation for off target effects triggered by these molecules. In addition the dsRNA triggered activation of a cell death pathway in the human lung cancer cell line studied suggests that TAK1-D might be a new and promising therapeutic target for the treatment of nonsmall cell lung cancer. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)535-542
Number of pages8
Issue number3
StatePublished - Mar 2008


  • Apoptosis
  • Cell cycle
  • TAK1
  • siRNA

ASJC Scopus subject areas

  • Molecular Biology


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