Ubiquitin-specific peptidase 1: assessing its role in cancer therapy

Reversible protein ubiquitination represents an essential determinator of cellular homeostasis, and the ubiquitin-specific enzymes, particularly deubiquitinases (DUBs), are emerging as promising targets for drug development. DUBs are composed of seven different subfamilies, out of which ubiquitin-specific proteases (USPs) are the largest family with 56 members. One of the well-characterized USPs is USP1, which contributes to several cellular biological processes including DNA damage response, immune regulation, cell proliferation, apoptosis, and migration. USP1 levels and activity are regulated by multiple mechanisms, including transcription regulation, phosphorylation, autocleavage, and proteasomal degradation, ensuring that the cellular function of USP1 is performed in a suitably modulated spatio-temporal manner. Moreover, USP1 with deregulated expression and activity are found in several human cancers, indicating that targeting USP1 is a feasible therapeutic approach in anti-cancer treatment. In this review, we highlight the essential role of USP1 in cancer development and the regulatory landscape of USP1 activity, which might provide novel insights into cancer treatment. Graphical abstract