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The E3 ligases engage in the malignancy of UM. a MiR-17-3p inhibits MDM2-mediated degradation of TP53 through the UPS. However, LncRNA PVT1 in UM could disturb miR-17-3p-mediated inhibition of MDM2. b SKP2-mediated degradation of CDKN1B through the UPS induces UM growth. c Hypoxia induces transactivation of HIF1A that could be degraded through VHL-mediated UPS in normoxia. d RNF2-mediated ubiquitination of histone H2A executes completely different regulation of downstream genes in UM versus other tissues. e MYCBP2 elevates the sensitivity of UM cells to Trail-induced apoptosis by conjugating to C-MYC. However, miR-92a-3p overexpressed in UM reduces the protein level of MYCBP2. See the article in pages 179–188.