B04
Understanding ubiquitylation and FATylation by UBA6 in lung cancer
Project Summary
UBA6 is an unusual member of the E1 family of activating enzymes for ubiquitin and ubiquitin-like proteins (Ubls) as it activates ubiquitin and the Ubl FAT10. We recently derived first crystal structures of UBA6, including that of a UBA6-FAT10 complex, and identified enzyme variants impaired in either ubiquitylation or FATylation. Furthermore, we demonstrated that proliferation in a panel of lung cancer cells critically depends on the respective presence of the gene encoding UBA6. These preliminary data lay the foundation to investigate the role of UBA6 in non-small cell lung cancer (NSCLC) by dissecting the underlying molecular mechanisms, and by generating tool compounds to test the potential for targeting UBA6.
