Ubiquitin-specific peptidase 4 (USP4)

Ubiquitin-specific peptidase 4 (USP4) is a multidomain cysteine protease within the deubiquitinating enzyme (DUB) family, responsible for removing monoubiquitinated and polyubiquitinated chains (such as K48 and K63 linkages) from substrate proteins. USP4 regulates several critical cellular processes, including signal transduction (in the NF-κB, TGF-β, and Wnt/β-catenin pathways), spliceosome activity, DNA repair via homologous recombination, and cell fate determination. It shuttles between the cytoplasm and nucleus and is tightly regulated by post-translational modifications (such as phosphorylation and ubiquitination). Aberrant USP4 expression or mutation is linked to the progression and poor prognosis of various cancers and immune disorders. Efforts are ongoing to develop selective USP4 inhibitors as novel therapeutics for cancer and inflammatory diseases[1][3][4][5][6][7].

Other names

USP4Ubiquitin specific protease 4UNPUnphubiquitin carboxyl-terminal hydrolase 4

Inhibition leads to increased ubiquitination and degradation of signaling proteins (e.g., BRCA1, TGF-β receptor, NF-κB pathway components), modulating cell survival, proliferation, and immune signaling[1][3][7].