USP7

USP7 (ubiquitin-specific protease 7, HAUSP) is a cysteine deubiquitinase that regulates protein stability by removing ubiquitin from diverse substrates involved in cell-cycle control, genome maintenance, and stress responses^[1][2]. Mechanistically, USP7 is a central component of the USP7-MDM2-p53 signaling axis, where it deubiquitinates both p53 and its negative regulator MDM2, thereby controlling p53-dependent transcriptional programs, cell-cycle arrest, and apoptosis^[3][4][5]. Under basal conditions, USP7 preferentially stabilizes MDM2, whereas alterations in USP7 activity can shift the balance of p53 signaling and cellular stress responses^[3][4]. Beyond p53 regulation, USP7 contributes to genome stability and chromatin-associated regulatory processes through deubiquitination of proteins involved in DNA damage responses and epigenetic control^[2][6]. Dysregulated USP7 expression or activity has been associated with multiple human cancers, where elevated USP7 function supports tumor initiation, progression, and survival pathways^[1][2][7]. Compared with related deubiquitinases, USP7 is distinguished by its extensive interaction network and its dual capacity to regulate both tumor suppressors and oncogenic factors within the same signaling circuitry^[3][7]. For experimental applications, selective USP7 inhibitors have been developed and shown to promote MDM2 degradation, activate p53 signaling, and induce cell-cycle arrest or apoptosis in cancer models, supporting the use of USP7 as a therapeutic target and mechanistic research tool^[1][8][9].