Bcl 2 Human (minus BH3 domain)

B-Cell Leukemia/Lymphoma 2 (BCL-2) is a protein encoded by the BCL2 gene in humans. It is the founding member of the BCL-2 family of regulator proteins, which play a crucial role in the regulation of apoptosis, or programmed cell death . The BCL-2 protein is primarily known for its ability to inhibit apoptosis, thereby promoting cell survival .

The BCL-2 protein derives its name from its association with B-cell lymphomas. It was first identified in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas . This discovery marked the beginning of understanding the role of BCL-2 in cancer biology.

BCL-2 is localized to the outer membrane of mitochondria, where it plays a pivotal role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins . The protein functions by blocking the release of cytochrome c and reactive oxygen species (ROS) from the mitochondria, which are essential signals in the apoptosis cascade .

The BCL-2 family includes both pro-apoptotic and anti-apoptotic proteins. The pro-apoptotic proteins, such as Bax and Bak, promote mitochondrial membrane permeabilization, leading to apoptosis. In contrast, BCL-2 and its relative BCL-Xl inhibit these pro-apoptotic proteins, thereby preventing apoptosis .

The BH3 domain is a critical region within the BCL-2 family proteins that mediates protein-protein interactions. BH3-mimetics are a class of compounds designed to mimic the BH3 domain, thereby inhibiting the function of anti-apoptotic BCL-2 proteins . These mimetics have shown promising results in clinical settings, particularly in the treatment of chronic lymphocytic leukemia (CLL) .

Aberrations in the BCL-2 gene have been implicated in various cancers, including melanoma, breast cancer, prostate cancer, chronic lymphocytic leukemia, and lung cancer . The overexpression of BCL-2 leads to increased resistance to apoptosis, contributing to tumor growth and resistance to chemotherapy . Additionally, BCL-2 has been associated with other diseases, such as schizophrenia and autoimmunity .

Given its central role in apoptosis regulation and cancer development, BCL-2 has become a significant target for cancer therapy. The development of BH3-mimetics, such as venetoclax, has provided new avenues for treating hematological malignancies . Venetoclax, the first BCL-2 inhibitor approved by the US Food and Drug Administration, has shown efficacy in treating patients with CLL who have the 17p deletion and have received prior therapy .