B-cell lymphoma 2 family proteins and Caspase 3 (Bcl-2/Caspase-3)

The Bcl-2 family proteins and Caspase 3 are integral components of the intrinsic (mitochondrial) pathway of apoptosis (StatPearls, 2023). The Bcl-2 family consists of pro-apoptotic members (e.g., Bax, Bak) and anti-apoptotic members (e.g., Bcl-2, Bcl-xL, Mcl-1) that act as a rheostat to control mitochondrial outer membrane permeabilization (UniProt P10415). When the balance shifts toward a pro-apoptotic state, cytochrome c is released from the mitochondria, triggering the activation of Caspase 3, a cysteine protease that serves as the primary executioner of programmed cell death (UniProt P42574; Cell Death & Diff, 1999). In various malignancies, the balance between these proteins is disrupted, often through the overexpression of anti-apoptotic members, leading to chemotherapy resistance (Nature Reviews Cancer, 2002). Therapeutic intervention primarily focuses on BH3 mimetics, such as Venetoclax, which selectively inhibit anti-apoptotic Bcl-2 proteins to restore the apoptotic response (FDA, 2016). Monitoring the cleavage of Caspase 3 and its substrates, such as PARP, is a standard method for evaluating the efficacy of these pro-apoptotic drugs (Journal of Biological Chemistry, 2001).

Other names

Bcl-2 familyCaspase-3CASP3Apoptotic signaling pathway componentsB-cell CLL/lymphoma 2 familyCPP32Apopain

BH3 mimetics bind to the hydrophobic groove of anti-apoptotic Bcl-2 family proteins, preventing them from sequestering pro-apoptotic proteins (Bax/Bak), which then form pores in the mitochondrial membrane to release cytochrome c and activate the executioner Caspase 3 cascade (Nature Reviews Drug Discovery, 2023).