Interleukin-1R-associated kinase 2 is a novel modulator of the transforming growth factor beta signaling cascade

The transforming growth factor beta (TGFbeta) pathway orchestrates an extensive transcriptional program that is important for many processes in the cell. For example, TGFbeta regulates cell cycle, migration, and epithelial-to-mesenchymal transition. The TGFbeta pathway has a dual role in cancer: it...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Molecular cancer research Ročník 8; číslo 4; s. 592
Hlavní autoři: Mullenders, Jasper, Fabius, Armida W M, van Dongen, Miranda M W, Kuiken, Hendrik J, Beijersbergen, Roderick L, Bernards, René
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.04.2010
Témata:
Active Transport, Cell Nucleus - genetics
Cell Line, Tumor
Down-Regulation - genetics
Gene Expression Regulation, Neoplastic - genetics
Genes, cdc - physiology
Genetic Testing
Humans
Interleukin-1 Receptor-Associated Kinases - genetics
Interleukin-1 Receptor-Associated Kinases - metabolism
Neoplasm Invasiveness - genetics
RNA, Small Interfering - genetics
Signal Transduction - genetics
Smad2 Protein - genetics
Smad2 Protein - metabolism
Transforming Growth Factor beta - genetics
ISSN:1557-3125, 1557-3125
On-line přístup:Zjistit podrobnosti o přístupu
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:The transforming growth factor beta (TGFbeta) pathway orchestrates an extensive transcriptional program that is important for many processes in the cell. For example, TGFbeta regulates cell cycle, migration, and epithelial-to-mesenchymal transition. The TGFbeta pathway has a dual role in cancer: it is involved in early-stage tumor suppression but also contributes to tumor progression by promoting invasion. To identify the novel genes involved in TGFbeta pathway signaling, we have performed a functional genetic loss-of-function screen. We screened a small interfering RNA library targeting 700 kinases and kinase-related genes in a TGFbeta-responsive reporter assay. Several genes were identified that upon knockdown could repress the reporter signal; among these are the two cellular receptors for TGFbeta. In addition to these two known components of the TGFbeta pathway, several genes were identified that were previously not linked to the TGFbeta signaling. Knockdown of one of these genes, the IRAK2 kinase, resulted not only in an impaired TGFbeta target gene response but also in a reduction of the nuclear accumulation and phosphorylation of SMAD2. In addition, suppression of interleukin-1R-associated kinase 2 expression led to a partial override of a TGFbeta-induced cell cycle arrest. Our data show that interleukin-1R-associated kinase 2 is a novel and critical component of TGFbeta signaling.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1557-3125
1557-3125
DOI:10.1158/1541-7786.MCR-09-0386