Abstract |
Although inactivating frameshift mutations in the Transforming growth factor beta receptor type 2 ( TGFBR2) gene are considered as drivers of microsatellite unstable (MSI) colorectal tumorigenesis, consequential alterations of the downstream target proteome are not resolved completely. Applying a click-it chemistry protein labeling approach combined with mass spectrometry in a MSI colorectal cancer model cell line, we identified 21 de novo synthesized proteins differentially expressed upon reconstituted TGFBR2 expression. One candidate gene, the TGF-ß family member Growth differentiation factor-15 (GDF-15), exhibited TGFBR2-dependent transcriptional upregulation causing increased intracellular and extracellular protein levels. As a new TGFBR2 target gene it may provide a link between the TGF-ß branch and the BMP/GDF branch of SMAD-mediated signaling.
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Authors | Jennifer Lee, Fabia Fricke, Uwe Warnken, Martina Schnölzer, Jürgen Kopitz, Johannes Gebert |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 6
Pg. e0131506
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 26114631
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- GDF15 protein, human
- Growth Differentiation Factor 15
- Receptors, Transforming Growth Factor beta
- Smad Proteins
- Protein Serine-Threonine Kinases
- Receptor, Transforming Growth Factor-beta Type II
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Topics |
- Colorectal Neoplasms
(genetics, metabolism, pathology)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Growth Differentiation Factor 15
(genetics, metabolism, pharmacology)
- HCT116 Cells
- Humans
- Protein Serine-Threonine Kinases
(genetics, physiology)
- Receptor, Transforming Growth Factor-beta Type II
- Receptors, Transforming Growth Factor beta
(genetics, physiology)
- Signal Transduction
(drug effects, genetics)
- Smad Proteins
(metabolism)
- Transcriptional Activation
(genetics)
- Up-Regulation
(drug effects, genetics)
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