Characterisation of USP31, the 3rd microtubule localising Deubiquitylase

Ubiquitylation is a reversible modification with a variety of roles ranging from governing protein homeostasis and trafficking to DNA damage and the immune response. A ubiquitin molecule is added on a substrate protein by an orchestrated cascade of reactions performed by the E1, E2 and E3 enzymes, while it is removed by the Deubiquitylases (DUBs). This work reports for the first time on a hitherto uncharacterised DUB enzyme, USP31. I identified USP31 in a screen for regulation of the MYCN oncogene in neuroblastoma. However, my initial characterisation showed that USP31 localises on microtubules and the centrosome. I proceeded to map the microtubule localising sequence of USP31 to the unstructured C-terminal of the protein. From that point, I developed a variety of cellular models in order to study its effect on microtubule network properties and the downstream processes they govern.