Identifying the Interactors of OTUD6B-2 That Are Important for Its Function on C-Myc

The complexity of molecular signaling pathways, particularly in cancer research, has made the proto-oncogene c-Myc a key focus due to its role as a master regulator of cellular processes such as growth, division, and apoptosis. Dysregulation of c-Myc is linked to various cancers, making it a highly sought therapeutic target despite challenges in directly inhibiting its function. Recent efforts have shifted towards indirect targeting methods, including BET inhibitors, cyclin-dependent kinase inhibitors, and siRNA formulations. A novel approach using PROTACs and the investigation of c-Myc-specific deubiquitinases (DUBs) has shown potential, particularly the emerging player OTUD6B-2. This study aims to identify and characterize interactors of OTUD6B-2 that modulate c-Myc's stability and activity. Preliminary findings reveal HERC5, an ISG15 ligase, as a key interactor, suggesting ISGylation as a crucial modification upstream of c-Myc ubiquitination. The study demonstrates that OTUD6B-2 is essential for tumor formation, given its role in regulating c-Myc, and underscores the importance of ISG15 in the polyubiquitination and degradation process of c-Myc. These insights into the regulatory network governing c-Myc provide a foundation for novel therapeutic strategies in cancer treatment. Future research will focus on elucidating the direct modification of c-Myc by ISG15 and its functional implications, to uncover new targets for cancer therapy.