Ubiquitin-specific protease 2 (USP2)

Ubiquitin-specific protease 2 (USP2) is a member of the ubiquitin-specific protease family of deubiquitinating enzymes. It is a cysteine protease that removes ubiquitin from polyubiquitinated protein substrates, thus rescuing them from proteasomal degradation and regulating their stability in the cell[6][8]. The human USP2 gene is located on chromosome 11q23.3 and produces multiple isoforms through alternative splicing, including USP2-45, USP2-69, USP2b, and others, which differ mainly in their N-termini but share a conserved catalytic core responsible for deubiquitination activity[2][3][9]. USP2 is highly conserved and widely expressed in various tissues, with roles in protein homeostasis, cell cycle progression, apoptosis, and other cellular processes[2][3]. It has been implicated in the development and progression of several cancers, notably prostate cancer, where it is frequently overexpressed and contributes to tumorigenesis by stabilizing oncogenic substrates such as fatty acid synthase[6][8]. USP2 is under investigation as a therapeutic target, with small-molecule inhibitors demonstrating anticancer activity in preclinical models[3]. Its central function in the ubiquitin-proteasome system is both a therapeutic opportunity and a challenge, as inhibition could affect essential processes in normal cells[5][6].

Other names

UBP41Ubiquitin carboxyl-terminal hydrolase 2USP2aUSP2bUSP2cUSP2-45USP2-69Usp2-1Usp2-2Usp2-3Usp2-4

Inhibition of deubiquitinase activity leading to increased ubiquitin-mediated proteasomal degradation, stabilization of substrates such as fatty acid synthase