USP7HAUSP

USP7HAUSP refers to the human ubiquitin-specific protease 7 (USP7), historically identified as herpesvirus-associated USP (HAUSP). USP7 is a cysteine protease in the ubiquitin-specific protease (USP) family and functions as a deubiquitinating enzyme that removes ubiquitin from substrate proteins, thereby affecting their stability and activity. The HAUSP designation originated from its interaction with herpes simplex virus 1 proteins; in humans it is commonly called USP7.

The protein has a modular structure consisting of an N-terminal TRAF-like regulatory domain, a central catalytic USP domain, and a C-terminal region containing ubiquitin-like (UBL) repeats. The TRAF-like domain mediates interactions with multiple partners, while the UBL repeats regulate catalytic activity and substrate recognition, contributing to subcellular localization and substrate specificity.

Biological roles of USP7 are diverse. It modulates the p53–MDM2 axis by deubiquitinating p53 and MDM2, a context-dependent action that can stabilize p53 or promote p53 degradation through MDM2 stabilization. Beyond this axis, USP7 participates in DNA damage response, cell cycle control, chromatin regulation, and immune signaling, reflecting its broad substrate range. It also interacts with viral proteins, illustrating a role in virus–host interactions.

Clinical significance and research focus on USP7 center on its role in cancer and viral infection. Dysregulation of USP7 can influence tumor suppressor pathways, making USP7 a target for anticancer strategies. Several small-molecule inhibitors (for example, P5091, P22077, and FT671) have shown preclinical activity by stabilizing p53 and promoting cancer cell death, and are under investigation for therapeutic potential.