USP5 and cancer: In addition, treatment with PYR41, a ubiquitin-activating enzyme E1 inhibitor, and MLN4924, an E3 ligase inhibitor, did not decrease total levels of p-STAT1/2, but markedly reduced the cytosolic p-STAT2 puncta as well as p-STAT1/2 levels in LEVs from USP5-depleted cancer cells (Figure 6C and Supplemental Figure 9, D and E).