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 journalArticle

4 Citations (Scopus)

Abstract

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
JournalRNA
Volume14
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Double-Stranded RNA
Apoptosis
Small Interfering RNA
p38 Mitogen-Activated Protein Kinases
Lung Neoplasms
Cell Line
Toll-Like Receptors
RNA Interference
Cell Cycle Checkpoints
Non-Small Cell Lung Carcinoma
Genes
Signal Transduction
Cell Death
Therapeutics

Keywords

  • Apoptosis
  • Cell cycle
  • siRNA
  • TAK1

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Sequence-specific activation of TAK1-D by short double-stranded RNAs induces apoptosis in NCI-H460 cells. / Kodym, Reinhard; Kodym, Elisabeth; Story, Micheal D.

In: RNA, Vol. 14, No. 3, 03.2008, p. 535-542.

Research output: Contribution to journalArticle

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