Figure 7
Schematic illustration for the action mechanisms of ABT-263-induced Mcl-1 upregulation in HCC cells. ABT-263 increases Mcl-1 mRNA level by augmenting its stability instead of transcriptional activation. Meanwhile, ABT-263 enhances Mcl-1 protein stability by regulating the phosphorylation status of Mcl-1. ERK- and JNK-mediated Mcl-1Thr163 phosphorylation contribute to ABT-263-induced Mcl-1 protein stability. Akt-mediated GSK-3β inactivation also plays important role in preventing Mcl-1 protein degradation in the presence of ABT-263. By increasing Mcl-1 stability at both mRNA and protein levels, ABT-263 induces Mcl-1 upregulation.