Supervisor Project : Investigation of linkage-selective Ub chain assembly and Ub binding in a yeast Ub ligase and its human homologue
Scientific Director, Institute of Molecular Biology (IMB), Mainz; Professor, Faculty of Biology, University of Mainz. She was group leader at the Cancer Research UK London Research Institute, Clare Hall Laboratories and Max Planck Institute for Terrestrial Microbiology. Helle was awarded with an ERC advanced grant, EMBO Young investigator, Member of EMBO since 2008 and BioFuture Prize from the German Federal Ministry of Education and Research.
As a model for polyUb interactors in yeast we will use a poorly characterised protein, Etp1, whose C-terminus binds K63-linked chains with high preference. The protein also harbours a RING domain characteristic of Ub ligases, and an additional ZnF-UBP Ub-binding domain, which usually requires Ub’s free C-terminus for interaction. Its human homologue, BRAP2, which shares this unusual domain arrangement, was initially isolated as a BRCA1 interactor and associates with two closely related de-ubiquitylation enzymes. Deregulation of BRAP2 has been linked to cancer and inflammatory disorders. However, the relevance of its Ub-interacting domains is completely unknown. In a combination of biochemical, cell biological and genetic approaches we will characterise the linkage selectivity of Etp1’s and BRAP2’s UBDs, elucidate their significance for the proteins’ Ub ligase activities and gain insight into their biological functions.