Posttranslational modification of proteins by ubiquitin or ubiquitin-like proteins (Ubls) plays a pivotal role in the regulation of a broad range of cellular processes including protein degradation, cell signaling, transcription and DNA damage response. Defects in the regulation of ubiquitin- and Ubl-mediated signaling have been linked to muscle wasting disorders, cancer, viral infection and neurodegeneration. Since ubiquitin and Ubls are involved in many essential cellular pathways, the enzymes that catalyze these modifications represent a critical area of basic research.
Our research interest is to determine the molecular mechanisms governing ubiquitination and Ubl-conjugation to cellular proteins. More than 700 enzymes are involved in these modifications and only little is known about their specificity, activity and interaction network. We pursue our interest by performing structure-function studies on these enzymes. The goal is to provide structural insight on the molecular mechanism of these enzymes that will help to identify new therapeutic targets.