Ubiquitin-specific protease 7 (USP7), a crucial member of the deubiquitinase family, regulates substrate protein stability to participate in diverse physiological and pathological processes. USP7 exhibits unique structural characteristics comprising an N-terminal TRAF domain, a catalytic domain, and C-terminal ubiquitin-like (UBL) domains. Notably, the dynamic transition mechanism between inactive and active conformations in the catalytic domain confers highly regulatable enzymatic activity. Physiologically, USP7 plays pivotal roles in cell cycle progression, DNA damage repair, and key signaling pathways through deubiquitinating critical regulatory factors. However, USP7 dysfunction triggers various diseases including cancers, metabolic disorders, neurodegenerative diseases, and Hao-Fountain syndrome. This review systematically summarizes structural features and physiological functions of USP7, elucidates its regulator mechanisms in disease pathogenesis, and evaluates currently reported USP7 targeted inhibitors and activators. These insights provide theoretical foundations for developing novel regulators and potential therapeutic strategies for related diseases.
Shi et al. (Fri,) studied this question.