Ubiquitin-specific peptidase 47 (USP47)

Ubiquitin-specific peptidase 47 (USP47) is a cysteine protease within the USP family, structurally related to USP7 and USP40[1]. It catalyzes removal of ubiquitin from Lys48- and Lys63-linked polyubiquitin chains, thereby regulating protein stability, signaling, and cellular homeostasis. USP47 is widely expressed, with highest abundance in the brain, liver, and kidneys, and localizes to cytoplasmic vesicles and intermediate filaments[1]. Biologically, USP47 stabilizes key proteins involved in axonal growth (katanin), cell adhesion (E-cadherin), EMT, and DNA repair (Pol β)[1][2]. It regulates signaling pathways (Hippo, p53, NF-κB, Wnt, and others) and is upregulated in many cancers, contributing to tumor development, metastasis, and resistance to therapy. Inhibition of USP47 can suppress cancer cell growth, reverse EMT, and impair DNA repair, making it a promising therapeutic target[1][3]. USP47 also participates in modulating immune responses by regulating inflammasome assembly and pro-inflammatory cytokine release, as well as maintaining genome integrity and neuronal development[2]. Therapeutic inhibition—e.g., with P22077—is in preclinical development and shows efficacy against drug-resistant leukemias and solid tumors[1]. USP47’s regulatory versatility makes it central to cancer biology, immunity, and neural function, though risks of off-target effects and safety concerns remain to be explored.

Other names

USP47Ubiquitin specific protease 47Ubiquitin carboxyl-terminal hydrolase 47

Inhibition of USP47 activity leads to reversal of malignant tumor behavior, increased apoptosis, impaired DNA repair, and reduced EMT and cell proliferation Targeting USP47 can sensitize tumors to chemotherapy/targeted therapy by eradicating drug-resistant cells and cancer stem/progenitor cells USP47 inhibitors impair NLRP3 inflammasome activation, reducing inflammatory cytokine release