Structural mechanisms underlying MYC ubiquitylation (A10)

• Subject Area: Anatomy and Physiology ; Biochemistry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514894665

We propose to determine the structural mechanisms of two distinctive E3 ligase-DUB pairings - the Cullin-RING-type E3 SCF-FBXW7 and USP-type DUB USP28, and the HECT-type E3 UBR5 and OTU-type DUB OTUD5 - that normally regulate the levels of c-MYC but are mutationally disrupted in colorectal cancers and NSCLCs. We will also obtain small molecule binders to tumor-mutant FBXW7 as a first step toward developing molecules restoring E3 ligase activity.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 387: Functionalizing the Ubiquitin System against Cancer - UbiQancer
• Applicant Institution: Technische Universität München (TUM)
• Project Head: Professorin Dr. Brenda Schulman