Supplementary Figure S1-S3 from Mcl-1 Degradation Is Required for Targeted Therapeutics to Eradicate Colon Cancer Cells

Figure S1. Regorafenib and sorafenib did not affect Mcl-1 mRNA expression but induced GSK3β-dependent Mcl-1 degradation. A transfected quadruple mutant in 4 putative phosphorylation sites (S121A/E125A/S159A/T163A) of Mcl-1 was resistant to regorafenib-induced ubiquitination and degradation. Figure S2. Apoptosis induced by regorafenib or sorafenib was suppressed in HCT116 cells with Mcl-1 phosphorylation site mutant knock-in (Mcl-1-KI), inhibition of GSK3β, or knockout of BAX. Figure S3. Mcl-1 degradation and PUMA induction did not affect each other in regorafenib-induced apoptosis. Regorafenib-induced apoptosis in Mcl-1-KI cells could not be restored by the Bcl-2/Bcl-XL inhibitors ABT-737 or ABT-263.