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USPs-mediated tumor stemness and hypoxic microenvironment Under normoxic conditions, HIF-1α is degraded via the ubiquitin-proteasome pathway. USP22 enhances the stability and transcriptional activity of HIF-1α under hypoxia through deubiquitination and induces upregulation of HIF-1α downstream genes. USP22 maintains cancer stemness by regulating BMI1 and β-catenin pathways. Furthermore, USP44 promotes prostate cancer stemness by deubiquitinating EZH2.
