The Bcl-2 Family Proteins: Insights into Their Mechanism of Action and Therapeutic Potential

The Bcl-2 family proteins are critical regulators of apoptosis at the mitochondria and endoplasmic reticulum. During apoptosis, cell fate is determined by complex protein–protein and protein–membrane interactions between the pro- and anti-apoptotic Bcl-2 family members. Commitment to apoptosis is marked by the permeabilization of the outer mitochondrial membrane, a step often considered as the point of no return for the cell. Inhibition of this step enables the survival and proliferation of cancers. Here we describe the mechanisms of regulation of this step by the Bcl-2 family of proteins and summarize progress in targeting Bcl-2 proteins as therapeutic targets for cancer.