Ubiquitin-specific-processing protease 47 (USP47) (USP47)

Ubiquitin-specific-processing protease 47 (USP47) is a cysteine protease belonging to the deubiquitinating enzyme (DUB) family, primarily responsible for removing ubiquitin moieties from substrate proteins to prevent their proteasomal degradation [1]. It plays a pivotal role in the base excision repair (BER) pathway by stabilizing DNA polymerase beta, thereby maintaining genomic integrity [2]. Additionally, USP47 regulates the stability of the transcription factor Snail, a key driver of epithelial-mesenchymal transition (EMT) and cancer metastasis [3]. In many cancers, including colorectal and lung carcinomas, USP47 is upregulated and associated with poor prognosis and resistance to DNA-damaging therapies [1,2]. Therapeutic strategies targeting the USP47 catalytic domain aim to promote the degradation of these oncogenic or repair-related substrates using small molecule inhibitors like P5091 or P22077 [4]. However, a major challenge in drug development is achieving high selectivity for USP47 over its close structural homolog, USP7, to minimize potential side effects [4].

Other names

Ubiquitin carboxyl-terminal hydrolase 47Deubiquitinating enzyme 47USP47

Inhibition of the deubiquitinating activity of the USP47 catalytic domain, leading to the polyubiquitination and subsequent proteasomal degradation of substrate proteins such as DNA polymerase beta and Snail [2,3].