Next, to further demonstrate the mechanism by which TRIM59 regulates STAT3 signaling by promoting macroH2A1 ubiquitination and degradation and inhibiting TC45 dephosphorylation in GBM, we compared the effects of exogenous TRIM59 WT, S308A, ΔR, or Y218F mutant on mH2A1 protein levels, p-STAT3, STAT3 binding with the PIM1 promoter, and PIM1 mRNA expression in LN229/EGFR/shTRIM59 GBM cells. The gene discussed is STAT3; the disease is glioblastoma.