Investigating common and distinct mechanisms of c-Rel and OTUD4 in lymphoma (P05)

• Subject Area: Hematology, Oncology ; Immunology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 360372040

Amplification of the NF-κB transcription factor c-REL genomic locus is frequently observed in lymphoma, but the consequences for B cell biology and lymphomagenesis remained enigmatic. We generated the first mouse models for c-Rel gain, which displayed increased germinal centre B cells and autoimmunity. We have also obtained evidence for novel post-transcriptional and post-translational regulation of c-Rel. In particular, the OTUD4 ubiquitin protease is a new vulnerability in lymphoma that mediates c-Rel stabilization and its nuclear localization. Here, we will analyse the molecular regulation of c-Rel and OTUD4 activity in detail, investigate the collaborative oncogenic network of c-Rel and dissect the c-Rel-OTUD4 axis as well as additional OTUD4 targets in lymphoma.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1335: Aberrant Immune Signals in Cancer
• Applicant Institution: Technische Universität München (TUM)
• Project Heads: Dr. Vanesa Fernández-Sáiz; Professor Dr. Marc Schmidt-Supprian