BCL-2, BCL-xL, and BCL-w (BCL-2, BCL-xL, BCL-w)

BCL-2, BCL-xL, and BCL-w are anti-apoptotic members of the BCL-2 protein family. They localize primarily to the mitochondrial outer membrane, where they regulate the intrinsic pathway of apoptosis by sequestering pro-apoptotic proteins and preventing mitochondrial outer membrane permeabilization. Their expression is crucial for normal tissue homeostasis but is frequently dysregulated in cancer, contributing to tumor cell survival and chemotherapy resistance. Pharmacological inhibition of these proteins—using so-called BH3 mimetics—restores apoptotic sensitivity and has become an important therapeutic strategy, particularly for certain hematologic malignancies

Other names

B-cell leukemia/lymphoma 2BCL2BCL2-like 1BCL2L1BCL2-like 2BCL2L2

Inhibition of anti-apoptotic activity, enabling activation of BAX/BAK and induction of apoptosis; BH3-mimetic binding to the hydrophobic groove, disrupting protein–protein interactions necessary for survival signaling