• Inhibition of B-RafV600E in melanoma cells by PLX4720 led to induction of the three Bim isoforms BimEL, BimL, and BimS, but the increase in BimS was the most profound.• The splicing factor SRp55 was responsible for the increased BimS splicing.• Dual treatment of PTEN-negative melanoma cells with PLX4720 and a PI3K inhibitor enhanced Bim expression and apoptosis.• Combining the B-Raf inhibitor vemurafenib with the MEK inhibitor trametinib increased Bim expression and apoptosis. Here, PPIB is linked to melanoma.