Date of Award

8-20-2024

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Science

First Advisor

Maurizio Bocchetta

Abstract

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.

Available for download on Tuesday, September 16, 2025

Included in

Oncology Commons

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