Function and targeting of membrane-bound E3 ligases in AML (A02)

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

Acute myeloid leukemia (AML), which continues to be characterized by poor overall survival, interacts with its microenvironment via various membrane proteins. Expression of some of these surface proteins are regulated by membrane-associated RING-CH (MARCH) E3 ubiquitin ligases. Despite their structural similarity, we identified differential expression of MARCH2 and 3 ligases in human AML cells and differences in their prognostic value for AML progression. Using various biochemical technologies and in vitro and in vivo assays the function and pathophysiological role of MARCH2 and 3 in AML will be validated and, eventually, proteolysis targeting chimeras (PROTACs) or antibodies (PROTABs) developed to target these membranous structures.

• 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. Ivan Dikic; Professorin Dr. Daniela Krause