USP7 at the Crossroads of Ubiquitin Signaling, Cell Cycle, and Tumorigenesis

Protein homeostasis is a dynamic process essential for cellular function and survival, tightly controlled by the ubiquitin–proteasome system. Within this system, ubiquitin-specific protease 7 (USP7) plays a key role as a deubiquitinating enzyme, thus modulating the stability, localization, and activity of a wide variety of substrates. USP7 is involved in critical cellular processes such as DNA repair, apoptosis, immune response, and epigenetic regulation. The dysregulation of USP7 expressions or activity has been linked to several pathological conditions, including cancer, neurodegenerative and inflammatory diseases, and viral infections. This enzyme exerts its biological functions through the stabilization of both oncogenic and tumor suppressor proteins, highlighting its sensitive role in tumorigenesis. Despite the identification of selective USP7 inhibitors with promising preclinical activity, the development of clinically effective compounds remains a major challenge. This review summarizes the current understanding of USP7 structure, function, and biological relevance, with a particular emphasis on its potential as a therapeutic target in oncology.