Understanding ubiquitylation and FATylation by UBA6 in lung cancer (B04)

• Subject Area: Hematology, Oncology ; Biochemistry ; Structural Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514894665

UBA6 activates ubiquitin and the ubiquitin-like protein FAT10, the first step in the site-specific modification of target proteins with ubiquitin or FAT10. Our preliminary data demonstrated a selective increase in FATylation in lung cancer patient samples, as well as an increase in FAT10 expression and abundance, compared to non-transformed tissue. Furthermore, a small panel of representative human non-small cell lung cancer cell lines did not tolerate loss of Uba6 or FAT10. Based on structural studies, UBA6 variants selectively impaired in ubiquitin or FAT10 activation were identified. Building on these preliminary data, the proposed studies will decipher the role of the UBA6 machinery in non-small cell lung cancer.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 387: Functionalizing the Ubiquitin System against Cancer - UbiQancer
• Applicant Institution: Technische Universität München (TUM)
• Project Heads: Professor Dr. Markus Elmar Diefenbacher; Professor Dr. Hermann Schindelin