Ubiquitin carboxyl-terminal hydrolase 22 (USP22) (USP22)

Ubiquitin carboxyl-terminal hydrolase 22 (USP22) is a cysteine protease and a key catalytic subunit of the SAGA (Spt-Ada-Gcn5 Acetyltransferase) complex, where it functions as a deubiquitinating enzyme (DUB) (UniProt, 2024). Its primary biological role involves the removal of monoubiquitin from histones H2B and H2A, a process essential for transcriptional activation and chromatin remodeling (NCBI Gene, 2024). Beyond its epigenetic functions, USP22 stabilizes critical non-histone proteins such as c-Myc, SIRT1, and Cyclin D1, thereby promoting cell cycle progression and preventing apoptosis (PubMed, 2021). In clinical oncology, USP22 is recognized as a core component of an 11-gene 'death-from-cancer' signature, with its overexpression strongly correlated with poor prognosis, metastasis, and therapeutic resistance in various malignancies (Nature Communications, 2020). While the protein is the primary functional target, USP22 mRNA is also a focus for therapeutic intervention using RNA-interference (RNAi) and antisense oligonucleotides to downregulate its expression in cancer cells (Journal of Experimental & Clinical Cancer Research, 2023). Experimental small-molecule inhibitors like WP1130 have demonstrated the potential to suppress USP22 activity, leading to the degradation of oncogenic substrates and inhibited tumor growth in preclinical models (Biochemical Pharmacology, 2019).

Other names

Ubiquitin-specific-processing protease 22Deubiquitinating enzyme 22USP22

Inhibition of the deubiquitinating activity of the USP22 enzyme, which leads to the accumulation of polyubiquitinated substrates and their subsequent degradation by the 26S proteasome, as well as the modulation of histone H2B ubiquitination to suppress oncogenic gene expression programs.