Ubiquitin specific peptidase 3 (USP3)

Ubiquitin specific peptidase 3 (USP3) is a deubiquitinating enzyme belonging to the ubiquitin-specific protease family. It functions by removing ubiquitin molecules from specific protein substrates, thereby preventing their proteasomal degradation and maintaining protein homeostasis[5]. USP3 is involved in several key biological processes, including regulation of the cell cycle, DNA damage repair (notably by deubiquitinating histone H2A and γH2AX at DNA damage sites), and innate immune signaling through stabilization of adapter proteins like ASC during inflammasome assembly[1][4][5]. Overexpression or dysregulation of USP3 has been implicated in the progression of various cancers, where it can promote proliferation, migration, and invasion of tumor cells—partly via stabilization of effectors such as EPHA2 and activation of the PI3K/AKT pathway[2]. USP3 is also involved in antiviral defense, such as inhibiting HIV-1 by stabilizing A3G, an intrinsic antiviral factor[3]. As a result, USP3 is being explored as a potential therapeutic target in oncology, immunology, and infectious diseases, though specific pharmacological inhibitors are not yet clinically available[5].

Other names

Ubiquitin carboxyl-terminal hydrolase 3Deubiquitinating enzyme 3Ubiquitin thioesterase 3Ubiquitin-specific-processing protease 3SIH003UBPUSP3

Inhibition of USP3 leads to increased ubiquitination and degradation of specific substrate proteins, affecting cell cycle progression, DNA repair, and immune signaling[2][5] Modulation of USP3 can alter inflammatory responses and cellular tolerance via targets such as ASC[1][5]