PMID:18230764
| Citation |
Kodym, R, Kodym, E and Story, MD (2008) Sequence-specific activation of TAK1-D by short double-stranded RNAs induces apoptosis in NCI-H460 cells. RNA 14:535-42 |
|---|---|
| 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 NFkappaB 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. |
| Links |
PubMed PMC2248254 Online version:10.1261/rna.738508 |
| Keywords |
Alternative Splicing; Apoptosis/drug effects; Base Sequence; Cell Line, Tumor; Enzyme Activation/drug effects; Humans; MAP Kinase Kinase Kinases/genetics; MAP Kinase Kinase Kinases/metabolism; MAP Kinase Signaling System; RNA/chemistry; RNA/genetics; RNA/pharmacology; RNA, Small Interfering/chemistry; RNA, Small Interfering/genetics; RNA, Small Interfering/pharmacology; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Transfection |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
References
See Help:References for how to manage references in EcoliWiki.