Fig. 3
From: Targeting MCL-1 in cancer: current status and perspectives
MCL-1 as a target for cancer therapy. a In normal cells, MCL-1 sequesters BH3-only proteins or neutralizes the effector proteins BAX and BAK, preventing cell death and maintaining cell survival. Various cell stress factors increase the expression of the special “activator” NOXA, subsequently replacing or preventing MCL-1 binding to BAX and BAK. BAX and BAK homo-oligomerize and form pores spanning the outer mitochondrial membrane to allow cytochrome C to be released into the cytoplasm, which triggers the activation of the caspase cascade and ultimately leads to cell apoptosis. b In malignant cells, overexpression of MCL-1 allows cancer cells to evade apoptosis by sequestering pro-apoptotic proteins. MCL-1 inhibitors selectively bind to MCL-1, freeing pro-apoptotic proteins, BAX/BAK, which initiates apoptosis