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

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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.