Helle ULRICH

Supervisor Project : Investigation of linkage-selective Ub chain assembly and Ub binding in a yeast Ub ligase and its human homologue

 

Partner Lab

The Institute of Molecular Biology Mainz (IMB) (www.imb.de) is a basic research
centre on the campus of Johannes Gutenberg University Mainz, Germany. Scientists at
IMB aim to understand the biology of the cell nucleus, focusing on epigenetic gene
regulation, genome stability and developmental processes. IMB hosts researchers from a
variety of backgrounds, ranging from biochemists, molecular and cell biologists to
computational biologists and physicists, thus fostering and international and
interdisciplinary atmosphere. IMB’s state-of-the-art Core Facilities provide access to
sophisticated equipment as well as training and expert advice from dedicated staff in
bioinformatics, cytometry, genomics, microscopy and proteomics.

About

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.

Summary of the Project

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.