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Upon stimulation of cells with transforming growth factor β (TGF-β), Smad proteins form trimeric complexes and activate a broad spectrum of target genes. It remains unresolved which of the possible Smad complexes are formed in cellular contexts and how these contribute to gene expression. By combining quantitative mass spectrometry with a computational selection strategy, we predict and provide experimental evidence for the three most relevant Smad complexes in the mouse hepatoma cell line Hepa1-6. Utilizing dynamic pathway modeling, we specify the contribution of each Smad complex to the expression of representative Smad target genes, and show that these contributions are conserved in human hepatoma cell lines and primary hepatocytes. We predict, based on gene expression data of patient samples, increased amounts of Smad2/3/4 proteins and Smad2 phosphorylation as hallmarks of hepatocellular carcinoma and experimentally verify this prediction. Our findings demonstrate that modeling approaches can disentangle the complexity of transcription factor complex formation and its impact on gene expression.
Pubmed ID: 29248373 RIS Download
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This monoclonal targets Raised against amino acids 1-552 representing full length Smad4 of human origin
View all literature mentionsThis monoclonal targets Phospho-Smad3 (Ser423/425) (C25A9) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-Smad2 (Ser465/467) (138D4) Rabbit mAb
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis polyclonal targets Smad4
View all literature mentionsThis monoclonal targets Smad3
View all literature mentionsThis monoclonal targets Smad2 (D43B4) XP Rabbit mAb
View all literature mentionsThis monoclonal targets Smad2 / 3
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsA software which acquires and processes data sets, primarily through the Xcalibur system.
View all literature mentionsCell line Hepa 1-6 is a Cancer cell line with a species of origin Mus musculus (Mouse)
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