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GRK 2243 "Understanding Ubiquitylation: From Molecular Mechanisms to Disease"

Project C6

TRIM ubiquitin ligases in MYC-dependent signaling to the innate immune system

Martin Eilers

This project originates from our work that aims to understand why MYC proteins are such potent oncogenes. While the usual answer is that they drive growth and proliferation of tumor cells, we found that pancreatic carcinoma cells depend on MYC only when they grow in an immune-competent cells (Krenz, Cancer Research 2021). This shows that the critical tumor-promoting function of MYC in this tumor entity is to enable tumors cells to escape killing by the immune system. Understanding the underlying mechanism showed that MYC controls the intracellular transport and degradation of double-stranded RNA and via this control prevents the presentation of tumor cell antigens on the surface of the tumor cells. This transport pathway is controlled by TRIM ubiquitin ligases and this project aims at understanding this control and its role in immune evasion of tumors.