Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Holnthoner, W; Pillinger, M; Groger, M; Wolff, K; Ashton, AW; Albanese, C; Neumeister, P; Pestell, RG; Petzelbauer, P.
Fibroblast growth factor-2 induces Lef/Tcf-dependent transcription in human endothelial cells.
J Biol Chem. 2002; 277(48):45847-45853
Doi: 10.1074/jbc.M209354200
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- Co-Autor*innen der Med Uni Graz
- Neumeister Peter
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- Abstract:
- Lef/Tcf proteins belong to a family of architectural transcription factors that control developmental processes and play an important role in oncogenesis. Classical activators of Lef/Tcf-dependent transcription comprise the Wnt family of proteins, which translocate beta-catenin into the nucleus and allow the formation of transactivation-competent Lef/Tcf-beta-catenin complexes. Here we show that in human endothelial cells fibroblast growth factor-2 (FGF-2) reduces GSK-3 activity and augments nuclear levels of beta-catenin. FGF-2 induced Lef/Tcf-dependent transcription of a cyclin D1-luciferase construct. Gel shift assays revealed binding of Tcf-4 as the only Lef/Tcf family member and of beta-catenin to the Lef/Tcf site in the cyclin D1 promoter. Cotransfection with a dominant negative Tcf-4 construct inhibited the FGF-2-induced cyclin D1 promoter activity. Overexpression of an uninhibitable GSK-3beta mutant resulted in partial inhibition of FGF-2-mediated cyclin D1 induction. The importance for cyclin D1 in FGF-2-induced angiogenesis in vivo is shown in cyclin D1(-/-) mice, where FGF-2-induced new vessel formation was significantly reduced compared with FGF-2-induced angiogenesis in cyclin D1(+/+) mice. In conclusion, FGF-2 is a novel modulator of Lef/Tcf-beta-catenin signaling in endothelial cells, suggesting that angiogenic properties of FGF-2 are at least in part mediated by Lef/Tcf-beta-catenin activation.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Nucleus - metabolism
- Cells, Cultured - metabolism
- Cyclin D1 - genetics
- Cytoskeletal Proteins - metabolism
- DNA-Binding Proteins - physiology
- Endothelium, Vascular - cytology
- Fibroblast Growth Factor 2 - physiology
- Glycogen Synthase Kinase 3 - metabolism
- Humans - metabolism
- Lymphoid Enhancer-Binding Factor 1 - metabolism
- Promoter Regions (Genetics) - metabolism
- Protein Binding - metabolism
- Protein Transport - metabolism
- Trans-Activators - metabolism
- Transcription Factors - physiology
- Transcription, Genetic - physiology
- beta Catenin - physiology