Research interests

In the last ten years my research group has focused on the role of protein ubiquitination in disease. To unravel the function of protein ubiquitination in disease development we use a variety of biochemical, molecular biological and cell-biological techniques including yeast two-hybrid, protein-protein interaction assays and proteomics. In 2005 we discovered a novel type of ubiquitination that targets a cysteine residue in the substrate protein. Since then my group has made other important contributions to the ubiquitin field among which the identification and characterization of the RING E3 ligase involved in the ubiquitination of the peroxisomal import receptor and establishing a novel mechanism of E2 enzyme regulation that involves binding of a co-activator protein. Since 2010 we use our expertise on protein ubiquitination to study the role of this protein modification in Angelman Syndrome, a severe neurological disorder caused by mutations in the UBE3A gene encoding the ubiquitin protein ligase E6AP (collaboration with prof. Elgersma, Erasmus MC). To carry out this work we have established in vitro and cellular ubiquitination assays, including a recently developed system in which we have reconstituted E6AP-dependent target ubiquitination in bacteria. Protein-protein interaction screens have led to the identification of several E6AP-interacting proteins. We are using our battery of in vitro and cellular assays to establish the in vivo function of these E6AP targets and determine their contribution to AS pathology.

 

specialisation

Biochemistry and molecular biology

Research output

  1. Insights into ubiquitin-conjugating enzyme/co-activator interactions from the structure of the Pex4p:Pex22p complex

    Research output: Contribution to journalArticleAcademicpeer-review

  2. A disulphide bond in the E2 enzyme Pex4p modulates ubiquitin-conjugating activity

    Research output: Contribution to journalArticleAcademicpeer-review

  3. Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model

    Research output: Contribution to journalArticleAcademicpeer-review

  4. Evolution of the SH3 Domain Specificity Landscape in Yeasts

    Research output: Contribution to journalArticleAcademicpeer-review

View all (80) »

ID: 53111