Characterisation of cellular factors that modulate VEGF IRES-dependent translation initiation

• Applicant: Professorin Dr. Antje Ostareck-Lederer
• Subject Area: Cell Biology
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 80749926

The vascular endothelial growth factor A (VEGF) is one of the most important regulators of both physiological and pathological angiogenesis. Expression of VEGF is tightly regulated at the transcriptional level, but little is known about its post-transcriptional control. The VEGF mRNA 5’UTR contains two independent internal ribosome entry sites (IRES) A and B, which are able to promote efficient translation in a 5’cap-independent manner. The project will focus on the identification and functional analysis of cellular factors that are required for VEGF IRES-driven initiation of translation as well as the function of the VEGF mRNA 3’UTR in this process in breast cancer cells. We will study the complex composition and/or post-translational modification(s) of individual factors that are of functional relevance in these complexes. The results of the in vitro and in vivo experiments will allow the elucidation of the mechanism by which translation is controlled in a VEGF IRES and 3’UTR-dependent manner. Newly characterised factors might represent potential therapeutic targets, which can be further analysed to identify compounds, which interfere with their function for VEGF expression in pathological angiogenesis.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Dirk Ostareck