B-cell lymphoma 2 protein, B-cell lymphoma-extra large protein, B-cell lymphoma-w protein (BCL-2, BCL-XL, BCL-w)

The BCL-2 family consists of evolutionarily conserved proteins, including BCL-2, BCL-XL, and BCL-w, which function as key regulators of apoptosis, primarily at the level of the mitochondrial outer membrane. These anti-apoptotic proteins inhibit cell death by binding to and sequestering pro-apoptotic BCL-2 family members, thereby preventing mitochondrial outer membrane permeabilization and cytochrome c release, a pivotal event initiating the intrinsic apoptosis pathway. Overexpression of these proteins is common in cancer and contributes to tumor progression and therapy resistance by promoting cell survival. Targeted drugs, particularly BH3 mimetics like venetoclax and navitoclax, bind the hydrophobic groove of these proteins, disrupt their interaction with pro-apoptotic effectors, and induce apoptosis in malignant cells. Tight regulation of BCL-2, BCL-XL, and BCL-w is essential for cellular homeostasis and survival, as imbalances contribute to oncogenesis, neurodegeneration, and other diseases[1][2][4][6].

Other names

B-cell lymphoma 2Bcl2Bcl2-like 1Bcl-xLBcl2-like 2BCL2L2

Small-molecule inhibition of anti-apoptotic activity (induces apoptosis by blocking BCL-2 family members' interaction with pro-apoptotic proteins); BH3 mimetic binding to the hydrophobic groove, liberating pro-apoptotic effectors; Promotion of mitochondrial outer membrane permeabilization (via inhibition of BCL-2/BCL-XL/BCL-w)