Figure 5
Sensitivity to PRMT5 inhibition is attenuated by overexpression of MDM4-FL or loss of p53. (A) (Left panel) Effect of MDM4-FL overexpression on proliferation of Z-138 cells following 3 or 6 days of GSK3203591 treatment with respect to gIC50, gIC100, and dEC50 parameters. Transduction of an EGFP construct was used as a negative control. (Right panel) Representative growth curves comparing % growth relative to Day 0 in Z-138 cells overexpressing MDM4-FL vs. EGFP treated with various doses of GSK3203591 for 6 days. (B) Western blot showing the effect of MDM4-FL overexpression on p53 and p21 protein levels in Z-138 cells following 4 days of 1 µM GSK3203591 (+) or DMSO (−) treatment. (C) Effect of MDM4-FL overexpression on G1 cell cycle phase in Z-138 cells following 4 days of treatment with DMSO, 50 nM, or 500 nM GSK3203591. (D) (Left panel) Effect of p53 knockout on proliferation in SW48 colon cancer cells following 10 days of GSK3203591 or GSK3326595 treatment with respect to EC50, gIC50, and gIC90 parameters. (Right panel) Representative growth curves comparing % growth relative to Day 0 in wild-type or p53 genetic knockout SW48 cells treated with various doses of GSK3203591 for 10 days. (E) Western blot showing the effect of p53 knockout on p53 and p21 protein levels in SW48 cells following a time course (3, 7, 8, or 11 days) of 500 nM GSK3203591 treatment.
