Activation of the TGF-β/Smad signaling pathway in oncogenic transformation by v-Rel
| Autor: | Henry R. Bose, Richa Tiwari, William Bargmann |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
TGF-β
Oncogene Proteins v-rel animal structures Reticuloendotheliosis Viruses Avian Rel/NF-κB Smad Proteins SMAD Biology Transformation Cell Line Mothers against decapentaplegic homolog 3 Transforming Growth Factor beta Virology Animals Transcription factor Oncogenesis Regulation of gene expression Transforming growth factor beta Cell Transformation Neoplastic Gene Expression Regulation embryonic structures Cancer research biology.protein v-Rel Signal transduction Chickens Receptors Transforming Growth Factor beta Smad3 Transforming growth factor Signal Transduction |
| Zdroj: | Virology. 413(1) |
| ISSN: | 1096-0341 |
| Popis: | v-rel, encoded by the avian reticuloendotheliosis virus, is an acutely transforming member of the Rel/NF-κB family of transcription factors. Transformation by v-Rel is mediated by the aberrant expression of genes that are normally regulated by Rel/NF-κB. Here, we demonstrate activation of the TGF-β/Smad signaling pathway in Rel transformation. RNA and protein levels of key TGF-β and Smad family members (TGF-β2, -β3, TGF-β type II receptor, and Smad3) are upregulated in v-Rel transformed cells with little to no change in c-Rel-expressing cells. Treatment of v-Rel transformed lymphoid cells with kinase inhibitors of the TGF-β receptor dramatically reduces soft agar colony formation whereas addition of TGF-β2 further promotes transformation. Moreover, Smad3 but not Smad2, is selectively activated as the downstream mediator of TGF-β signaling. Blocking Smad3 expression or activity inhibits the oncogenic potential of v-Rel. Overall, TGF-β/Smad signaling is activated at multiple levels and is required for the transforming ability of v-Rel. |
| Databáze: | OpenAIRE |
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