The Ubiquitin System: From Signalling to Cancer

Research in our laboratory focuses on studying the molecular mechanisms through which the ubiquitin system controls cell growth and proliferation and understanding how deregulation of this network contributes to malignant transformation. We are especially interested in the role of Cullin-RING complexes, the largest class of E3 ubiquitin ligases in eukaryotes. Cullin-RING ubiquitin ligases (CRLs) share a common catalytic core consisting of a Cullin scaffold and a RING protein which functions as the docking site for ubiquitin conjugating enzymes. The catalytic core of CRL assembles with numerous substrate receptors, which target specific substrates for ubiquitylation. Due to the great diversity of their substrate receptor subunits, over 350 distinct CRLs are present in eukaryotic cells, establishing these enzymes as major mediators of ubiquitin conjugation and key regulators of a wide array of biological processes. Despite their importance, our knowledge of the biological functions, mechanism of action, regulation and physiological partners for most CRLs remains poor. Moreover, the majority of CRLs remains with no established substrates. Therefore, the major goal of our research program is to study the functions of orphan CRLs and systematically identify their biologically significant substrates as well as investigate how deregulation of CRL-mediated ubiquitylation leads to aberrant cell growth and oncogenesis.