Ubiquitin-specific peptidase 22 (USP22)

Ubiquitin-specific peptidase 22 (USP22) is a highly conserved deubiquitinating enzyme (DUB) that is part of the mammalian SAGA chromatin-modifying complex[4][6]. USP22 catalyzes the removal of ubiquitin from key histone proteins (H2A, H2B), regulating gene transcription, and from other non-histone targets implicated in cell cycle progression, apoptosis, stem cell differentiation, and immune response[1][4][6][7]. USP22 is abnormally expressed in multiple human cancers and is implicated in tumor development, cancer cell proliferation, drug resistance, and immune evasion[2][7]. Mechanistically, USP22 modulates key transcription factors, proto-oncogenes, and immune checkpoints including SIRT1, c-Myc, BMI-1, p53, and PD-L1[1][2][4][7]. High USP22 levels are associated with poor prognosis and therapy resistance, marking USP22 as both a biomarker and promising therapeutic target in oncology, although drug development is complicated by its central role in transcriptional and cellular homeostasis[7].

Other names

Ubiquitin carboxyl-terminal hydrolase 22USP22KIAA1063USP3LDeubiquitinating enzyme 22Ubiquitin thioesterase 22Ubiquitin-specific-processing protease 22Ubiquitin specific protease 22Ubiquitin thiolesterase 22

Inhibition of USP22 enzymatic activity (block deubiquitination) Modulate histone ubiquitination to alter transcriptional programs Suppress cancer cell growth, induce apoptosis/senescence Promote immune cell activation/reduce PD-L1 stabilization Reverse drug resistance (such as EGFR-TKI in lung cancer)