Reprogramming of the E3 ligase/DUB network during oncogenic transformation (A07)

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

One central mechanism which is altered during oncogenic transformation within tumor cells is the ubiquitin proteasome system. Our preliminary data demonstrates that NSCLC restructure the UPS system and discreet enzymes are either enriched or downregulated to accommodate for oncogenic transformation. Here, we identified USP10 as a selective increased DUB in NSCLC. Furthermore, by using cis-genetic CRISPR based screens we identified the E3-ligase KEAP1 as a common vulnerability for NSCLC, which is a dogma-breaking observation that holds great potential for future therapeutic interventions. Given the preliminary data presented the proposal sheds new light on the early mechanisms of cancer cell adaptation and unravels new biology on dependencies 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. Ivan Dikic