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. 2019 Aug 22;116(36):17990–18000. doi: 10.1073/pnas.1901323116

Fig. 5.

Fig. 5.

CDK4 and PRMT5 inhibition suppresses MDM4 expression by altering its mRNA splicing . (A) Western blots on cell lysates after 6-d treatment with 2 μΜ palbociclib, 500 nM (A375) or 250 nM (HT144) GSK3326595, or combination of both. (B and C) Proliferation curves of acquired-resistant cells expressing shMDM4 or shControl with or without treatment with 2 μM palbociclib grown in media containing 10 ng/mL doxycycline. Graphs are representative of 3 independent experiments. Error bars represent SEM for 3 technical replicates. (D) Western blots on lysates from resistant cells expressing shMDM4 or shControl grown for 48 h in media containing 10 ng/mL doxycycline. (E) Western blots on melanoma cell line lysates. (F and G) Proliferation curves of C002AR and A11AR cells treated with 2 μM palbociclib, 500 nM GSK3326595, or combination of both drugs. Graphs are representative of 3 independent experiments. Error bars represent SEM for 3 technical replicates. (H) PCR products showing the expression patterns of MDM4-FL and MDM4-SL mRNA in melanoma cell lines treated with 2 μΜ palbociclib, 500 nM (A375, CHL1, C067, D04) or 250 nM (HT144) GSK3326595, or combination of both drugs for 6 d. (I) Western blots on melanoma cell lines lysates treated as in H with or without treatment with 1 μΜ MG-132 added 16 h prior to experiment end point.