Hypusine - dependent molecular function of EIF5A in malignant transformation
Description: The eukaryotic intiation factor 5A (eIF-5A) is the only known cellular protein that contains the unusual amino acid hypusine. Hypusination of eIF5A is catalyzed by sequential action of deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). Hypusinated eIF5A affects multiple steps of mRNA translation and, in mammalian cells, participates in the transport of specific mRNAs. These activities promote aberrant cell proliferation, diabetic inflammation and HIV-1 production. However, the molecular basis of eIF5A function in these critical cellular processes remains a mystery and the cellular pathways that are influenced by hypusine formation are largely unknown. The research proposed here combines molecular- and cell biology methods with biochemistry, functional genomics, and mouse genetic approaches to characterize the molecular pathways which are controlled by the hypusine modification system. In particular, we will focus on understanding the molecular basis for this system’s role in malignant transformation. We will study hypusine-dependent translational control in normal cells and after oncogene driven transformation, explore the in vivo importance of hypusination in new conditional mouse models, and characterize the subset of mRNAs which are regulated via the hypusination state of eIF5A. A close interaction and the exchange of technologies and materials between both investigators will allow efficient progress and mutual enrichment of these projects. Scientifically, our combined efforts will result in a significant advancement of our understanding of the function of the hypusine modification system for cancer biology, as well as the potential value of targeting this system for cancer treatment.
Amount: CHF 439,000
Funding type: research
Funder scheme: Project funding
Start date: 2014-01-01
End date: 2017-10-31
Investigator: Balabanov, Stefan
Institution: University of Zurich – ZH
Subfield: Molecular Biology
Domain: Life Sciences
Funded outputs count: 4
Funder award ID: 150066
OpenAlex ID: G1809011541